Dendritic Protein Research Articles

Synapse specificity and long-term information storage.

The dendrites of a typical neuron in the central nervous system bear at least 1000 postsynaptic specializations indicating that in principal the individual neuron can process and store many bits of information. Electrophysiological experiments have also revealed that anatomically isolated groups of synapses on the same cell can separately process plastic events. Finally, many studies of behavioral and synaptic plasticity have demonstrated that long-lasting changes in synaptic transmission and behavior require both gene transcription and mRNA translation. To understand long-term information storage, then, the problem is to determine how the potentiated (or depressed) synapses of a single neuron become selectively modified during the long-lasting phases of synaptic plasticity. That is, how do the products of transcription and/or translation reach the modified synaptic sites without affecting the unmodified sites within the same neuron? There are at least three ways this could occur, including the selective capture of broadly distributed newly synthesized proteins by potentiated sites, the selective transport of newly synthesized proteins to potentiated sites, and the site-specific local production of new proteins by dendritic protein synthesis machinery (Figure 1; reviewed bySossin 1996; Goelet et al. 1986).

Cyclooxygenase-2 expression during rat neocortical development and in Rett syndrome

Cyclooxygenase or prostaglandin endoperoxide H synthase-2 (PGHS-2) is the first enzyme in the prostanoid biosynthetic pathways and, in brain, it is regulated as an immediate-early gene (IEG). PGHS-2 mRNA and protein are rapidly induced by physiological synaptic activity, and high basal expression in cerebral cortex appears to be maintained by the natural synaptic activity. In contrast to other IEGs, PGHS-2 is a dendritic protein that is enriched in dendritic spines and is, therefore, likely to play a direct role in synaptic physiology. Consistent wish a signaling function in mature dendritic spines, PGHS-2 expression is strongly regulated during normal postnatal development in the rat, with peak expression during the third and fourth weeks. Here we use immunocytochemical approaches to compare the developmental expression of PGHS-2 in rat neocortex with that of other well characterized markers of dendritic maturation. PGHS-2 immunoreactivity (ir) follows histogenetic gradients and expression in secondary or more distal dendrites postdates that of even the most delayed dendritic proteins. This developmental pattern parallels the critical period for somatosensory and visual cortex development. Accordingly, PGHS-2-ir may be a useful marker of the final activity-dependent stages of cortical development. Consistent with this potential histochemical utility, we demonstrate that the normal laminar pattern of PGHS-2-ir in human cortex is altered in patients with Rett syndrome, a form of mental retardation with known alterations of dendritic maturation. Further studies of the developmental expression of PGHS-2 in human cortical development may permit analyses of dendritic abnormalities, in syndromes associated with disturbances of activity-dependent development, as well as provide an anatomic basis for understanding the role of prostaglandin signaling in cortical development.

Characterization and sleep deprivation‐induced expression modulation of dendrin, a novel dendritic protein in rat brain neurons

Characterization and sleep deprivation‐induced expression modulation of dendrin, a novel dendritic protein in rat brain neurons

Characterization and sleep deprivation-induced expression modulation of dendrin, a novel dendritic protein in rat brain neurons.

We report on the characterization of the novel rat brain protein dendrin which is encoded by the brain-specific transcript 464. On immunoblots, two protein variants (81 kD, 89 kD) were identified in cytosolic and membraneous protein fractions. The variants are most abundant in the hippocampus, notably in apical dendrites of CA1 pyramidal cells. Dendritic and perikaryal immunolabelling is apparent in neurons of the cerebral cortex, dentate gyrus, subiculum, amygdala, and preoptic areas. In cortical and hippocampal dendrites, electron-dense immunoreaction is associated with the endoplasmic reticulum, the plasma membrane, and spine heads. An association of dendrin with polyribosomes and the presence of its mRNA in dendrites both provide evidence for dendritic mRNA translation. In the rat forebrain, dendrin expression is altered after an extended period of wakefulness. Twenty-four-hour sleep deprivation decreases the mRNA and protein concentrations of both variants in subcortical forebrain plus midbrain areas by 24 +/- 11% (P < 0.05) and 40 +/- 14% (P < 0.1), respectively, as measured relative to beta-actin mRNA and neural actin. In the cerebral cortex and hippocampus, the relative mRNA level remains unchanged whereas the cortical protein concentration is reduced by 42 +/- 10% (P < 0.05). Thus, dendrin belongs to a new class of dendritic proteins whose expression is differentially modulated by prolonged behavioral activity.

Protein Synthesis within Dendrites: Glycosylation of Newly Synthesized Proteins in Dendrites of Hippocampal Neurons in Culture

There is increasing evidence that certain mRNAs are present in dendrites and can be translated there. The present study uses two strategies to evaluate whether dendrites also possess the machinery for protein glycosylation. First, precursor labeling techniques were used to conjunction with autoradiography to visualize glycosyltransferase activities that are characteristic of the rough endoplasmic reticulum (RER) (mannose) or the Golgi apparatus (GA) (galactose and fucose) in dendrites that had been separated from their cell bodies and in intact neurons treated with brefeldin A or low temperature. Second, immunocytochemical techniques were used to define the subcellular distribution of proteins that are considered markers of the RER (ribophorin I) and GA (p58, alpha-mannosidase II, galactosyltransferase, and TGN38/41). Autoradiographic analysis revealed that isolated dendrites incorporated sugar precursors in a tunicamycin-sensitive and protein synthesis-dependent manner. Moreover, when intact neurons were pulse-labeled with 3H-labeled sugars at low temperature or after treatment with brefeldin A, labeling was distributed over proximal and sometimes distal dendrites. Immunolabeling for RER markers was predominantly localized in cell bodies but extended for a considerable distance into dendrites of all neurons. Immunolabeling for GA markers was confined to the cell body in approximately 70% of the neurons, but in 30% of the neurons, the staining extended into proximal and middle dendrites. These results indicate that the machinery for glycosylation extends well into dendrites in many neurons.

Identification of cytoskeletal proteins in the antennae of the silkmoths Antheraea polyphemus and A. pernyi.

Although the overall cytoskeletal morphology of the olfactory dendrite in the antennae of the silkmoths Antheraea polyphemus and A. pernyi is known, the cytoskeleton proteins that structurally and functionally support these structures remain to be identified in this paper, we describe the identification of tubulin, actin and intermediate filament-like proteins in the olfactory dendrites, and motor proteins such as kinesin and unconventional myosin in the antennal branches by the use of antibodies. We also show that the tubulins within the olfactory dendrites and in the antennal branches are acetylated. This study provides valuable information concerning the possible role of these proteins in transduction, transport and motility, as is evident in other systems.

Selective vulnerability of hippocampal CA3 neurons to hypoxia after mild concussion in the rat

Immunohistochemical staining for microtubule-associated protein 2 (MAP2) and synaptophysin was used to investigate the effect of hypoxia on hippocampal neurons after mild concussion in the rat. Male Sprague-Dawley rats were divided into four groups: Group 1 (n = 3) was subjected to a mild impact-acceleration closed head injury, group 2 (n = 3) was subjected to 30 min of moderate hypoxia, group 3 (n = 5) was subjected to head trauma followed by 30 min of moderate hypoxia, and group 4 (n = 3) comprised sham-operated controls. All rats were fixed by transcardial perfusion 24 h after insult. No damage was observed in CA1 or CA2 neurons in any of the rats. However, rats in group 3 showed selective damage of hippocampal CA3 neurons manifested by a pycnosis and a marked decrease in MAP2 immunoreactivity. Presynaptic terminals visualized by synaptophysin immunostaining showed no differences among groups. The loss of immunoreactivity for the post-synaptic somal and dendritic protein marker MAP2 from the CA3 subfield 24 h after combined insults indicates an increased vulnerability of pyramidal cells in this brain area.

Cerebellar granule cells in vitro recapitulate the in vivo pattern of GABA A-receptor subunit expression

GABA A-receptor heterogeneity is based on the combinatorial assembly of a family of 15 subunits (αl–6, β1–3, γ 1–3, δ, ϱ1–2) into multiple receptor subtypes. The factors regulating the differential expression of GABA A-receptor subtypes in the CNS are largely unknown. In the present study, we have used primary cultures of rat cerebellar granule cells as model system to analyze to which extent the expression, subunit composition, and subcellular localization of GABA A-receptors depend on signals available in the cerebellum in vivo, in particular GABAergic input which is lost in vitro. GABA A-receptor subunits were visualized immunchistochemically with subunit-specific antibodies and their subcellular localization was investigated by confocal laser microscopy with selective markers for dendritic proteins (microtubule-associated protein 2, non-phosphorylated neurofilaments) and synaptic vesicles (synaptophysin). Triple immunofluorescence staining experiments revealed that dissociated granule cells taken from 7-day-old rats and maintained in culture for 9 days co-expressed the subunits α1 α6 β2,3 γ2 δ, a subunit repertoire which is identical to that seen in vivo in the adult cerebellum. GABA A-receptor subunits were localized selectively in granule cell somata and in proximal neurites immunopositive for MAP-2. No staining was detected in distal neurites immunopositive for neurofilaments. GABA A-receptor subunits frequently were aggregated in clusters closely apposed to synaptophysin-immunoreactive varicosities, suggesting a post-synaptic localization. Thus, major functional determinants of GABA A-receptors in granule cells (subunit repertoire, subcellular segregation and clustering in post-synaptic sites) develop in vitro, indicating that they are regulated to a large extent by intrinsic factors, independently of GABAergic input.

A Regulatory Role for Sphingolipids in Neuronal Growth: INHIBITION OF SPHINGOLIPID SYNTHESIS AND DEGRADATION HAVE OPPOSITE EFFECTS ON AXONAL BRANCHING

Sphingolipids, particularly gangliosides, are enriched in neuronal membranes where they have been implicated as mediators of various regulatory events. We recently provided evidence that sphingolipid synthesis is necessary to maintain neuronal growth by demonstrating that in hippocampal neurons, inhibition of ceramide synthesis by Fumonisin B1 (FB1) disrupted axonal outgrowth (Harel, R. and Futerman, A. H. (1993) J. Biol. Chem. 268, 14476-14481). We now analyze further the relationship between neuronal growth and sphingolipid metabolism by examining the effect of an inhibitor of glucosylceramide synthesis, D-threo-1-phenyl-2-decanoylamino-3-morpholino-1- propanol (PDMP) and by examining the effects of both FB1 and PDMP at various stages of neuronal development. No effects of FB1 or PDMP were observed during the first 2 days in culture, but by day 3 axonal morphology was significantly altered, irrespective of the time of addition of the inhibitors to the cultures. Cells incubated with FB1 or PDMP had a shorter axon plexus and less axonal branches. FB1 appeared to cause a retraction of axonal branches between days 2 and 3, although long term incubation had no apparent effect on neuronal morphology or on the segregation of axonal or dendritic proteins. In contrast, incubation of neurons with conduritol B-epoxide, an inhibitor of glucosylceramide degradation, caused an increase in the number of axonal branches and a corresponding increase in the length of the axon plexus. A direct correlation was observed between the number of axonal branch points per cell and the extent of inhibition of either sphingolipid synthesis or degradation. These results suggest that sphingolipids play an important role in the formation or stabilization of axonal branches.

Cytochemical polarity in lateral geniculate interneurons

To determine the cytochemical composition of presynaptic dendrites, we have examined the distribution of synapsin 1, calcium and calmodulin-dependent protein kinase II (CaM-II), microtubule-associated protein 2 (MAP-2) and spectrin in cat lateral geniculate (LGN) class III cells by immuno-EM. Special attention was paid to the dendrites of these interneurons because they are both pre- and postsynaptic. The dendritic proteins MAP-2 and RBC spectrin were not observed in interneuron dendrites but these proteins were localized in relay cell dendrites. The synaptic vesicle-associated protein synapsin 1 was present in all synaptic vesicle containing profiles, including dendritic terminals. CaM-II, the major postsyaptic density protein, was found in all dendrites. Thus, the LGN interneuron dendritic compartment displays both axonal and dendritic cytochemical properties. The results suggest the possibility of unique molecular interactions in interneuron dendritic terminals.

Differential distribution of tau proteins in developing cat cerebellum

The differential distribution and phosphorylation of tau proteins in cat cerebellum was studied with two well characterized antibodies, TAU-1 and TAU-2. TAU-1 detects tau proteins in axons, and the epitope in perikarya and dendrites is masked by phosphorylation. TAU-2 detects a phosphorylation-independent epitope on tau proteins. The molecular composition of tau proteins in the range of 45 kD to 64 kD at birth changed after the first postnatal month to a set of several adult variants of higher molecular weights in the range of 59 kD to 95 kD. The appearance of tau proteins in subsets of axons corresponds to the axonal maturation of cerebellar local-circuit neurons in granular and molecular layers and confirms previous studies. Tau proteins were also identified in synapses by immunofluorescent double-staining with synapsin I, located in the pinceau around the Purkinje cells, and in glomeruli. Dephosphorylation of juvenile cerebellar tissue by alkaline phosphatase indicated indirectly the presence of differentially phosphorylated tau forms mainly in juvenile ages. Additional TAU-1 immunoreactivity was unmasked in numerous perikarya and dendrites of stellate cells, and in cell bodies of granule cells. Purkinje cell bodies were stained transiently at juvenile ages. During postnatal development, the intensity of the phosphate-dependent staining decreased, suggesting that phosphorylation of tau proteins in perikarya and dendrites may be essential for early steps in neuronal morphogenesis during cat cerebellum development.

Membrane traffic in polarized neurons in culture.

Fetal hippocampal neurons develop axons and dendrites in culture. To study how neurons form and maintain different plasma membrane domains, hippocampal neurons were infected with RNA viruses and the distribution of the viral glycoproteins was analyzed by light and electron microscopy. Infection of hippocampal cells with vesicular stomatitis virus (VSV) and fowl plague virus (FPV) resulted in the polarized distribution of the newly synthesized viral glycoproteins. The VSV glycoprotein appeared firstly in the Golgi apparatus and then in the dendrites. In contrast, the hemagglutinin of FPV, after accumulation in the Golgi apparatus, moved to the axons. These results suggest that the mechanism of sorting of viral glycoproteins might be similar in neurons and MDCK cells, a cell line of epithelial origin. In these cells the VSV glycoprotein and the hemagglutinin of FPV distribute to the basolateral and apical membranes, respectively. Transport of viral glycoproteins to both neuronal domains was microtubule dependent. Nocodazole treatment of infected neurons inhibited the delivery of axonal and dendritic viral glycoproteins equally. To investigate if the analogy between epithelial cells and neurons extended to include an endogenous plasma membrane protein, the distribution of Thy-1, a GPI-linked protein, was analyzed. By immunofluorescence and immunoelectron microscopy, Thy-1 was found exclusively along the axonal surface. In epithelial cells GPI-anchored proteins are located apically. The existence of a barrier on the neuronal plasma membrane that would prevent intermixing of axonal and dendritic proteins was analyzed by a liposomefusion assay.(ABSTRACT TRUNCATED AT 250 WORDS)

Pairing the cholinergic agonist carbachol with patterned Schaffer collateral stimulation initiates protein synthesis in hippocampal CA1 pyramidal cell dendrites via a muscarinic, NMDA-dependent mechanism

Effects of afferent stimulation on local synthesis of protein in CA1 pyramidal cell dendrites were studied using light microscope autoradiography. Tissue was fixed with paraformaldehyde immediately after 3 min exposure to 3H-leucine in order to trap 3H associated with macromolecules. The rate of 3H-leucine incorporation into dendrites of resting hippocampal slices was 10% the rate of incorporation into cell somata. Ninety percent of the incorporation into the somata was inhibited by cycloheximide (300 microM); none of the incorporation into dendrites was blocked by cycloheximide. Thus, there is no measurable extramitochondrial synthesis of protein in the dendrites of the resting slice. Slices were exposed to 50 microM carbachol and the Schaffer collateral afferents to the CA1 pyramidal cells were stimulated intermittently at 10 Hz over a 20 min period. In this case, 3H incorporation into dendrites was increased almost threefold over resting levels, with no effect on label over the cell somata. There was no associated increase in uptake of free 3H-leucine, and the increase in label was completely blocked by cycloheximide. Thus, associating carbachol and afferent stimulation appears to activate de novo protein synthesis in the dendrites. Neither the carbachol alone nor the Schaffer collateral stimulation alone increased synthesis. The activation of dendrite synthesis was completely blocked by 5 microM atropine, and also by 50 microM D-aminophosphonovalerate. It did not occur when carbachol was paired with steady stimulation of the Schaffer collaterals at 1 Hz for 20 min, rather than with the patterned high-frequency stimulation. Thus, associating a cholinergic agonist with a level of neural activity that occurs in CA3 and CA1 pyramidal cells during exploratory behavior (Muller et al., 1987) initiates local protein synthesis in target dendrites. This effect is dependent on muscarinic cholinergic receptors and NMDA-type glutamate receptors. The possible relationship of this phenomenon to mechanisms of learning is discussed.

Neuropathologic changes in the gerbil brain after chronic hypoperfusion.

An animal model has been developed to elucidate the pathological changes in brain cytoskeletal proteins during chronic hypoperfusion. Newly designed coiled clips were placed around both carotid arteries of Mongolian gerbils (n = 10) to cause stenosis without occlusion. Those gerbils showing impaired learning ability by the passive avoidance paradigm were killed for neuropathologic study after 12 weeks. The brains showed ventricular dilatation, cortical atrophy, and rarefaction of the white matter. Immunoreactivity to anti-microtubule-associated protein 2 antibody in the cerebral cortex and the hippocampus was diminished, indicating dendritic changes of neurons. In the thalamic axonal regions, staining with anti-neurofilament 200K protein antibody was increased, suggesting increased amounts of neurofilament proteins or increased phosphorylation of the protein. Increased immunoreactivity to anti-glial fibrillary acidic protein antibody was observed in a wedge-shaped configuration, corresponding to the border zone of perfusion by small vessels. These findings suggest that changes in the cytoskeletal proteins in dendrites, axons, and glial cells may cause neuronal death under conditions of chronic cerebral hypoperfusion.

Cleavage of bovine brain microtubule-associated protein-2 by human immunodeficiency virus proteinase.

The high-molecular-weight dendritic cytoskeletal protein known as microtubule-associated protein (MAP)-2 displays the capacity to stimulate tubulin polymerization and to associate with microtubules. Serine proteases cleave MAP-2 into a C-terminal M(r) 28,000-35,000 microtubule-binding fragment and a larger N-terminal M(r) 240,000 projection-arm region. We now show that human immunodeficiency virus (HIV) proteinase also progressively degrades purified MAP-2 in vitro. This proteolysis reaction is characterized by transient accumulation of at least six intermediates, and most abundant of these is an M(r) 72,000 species that retains the ability to associate with taxol-stabilized microtubules. Treatment of this M(r) 72,000 species with thrombin releases the same M(r) 28,000 component as that derived from thrombin action on intact high-molecular-weight MAP-2, indicating that the viral aspartoproteinase action preferentially occurs further toward the N-terminus. The association of the M(r) 72,000 component with microtubules can be disrupted by the presence of a 21-amino acid peptide analogue of the second repeated sequence in the MAP-2 microtubule-binding region. We also studied HIV proteinase action on MAP-2 in the presence of tubulin and other MAPs that recycle with tubulin, and contrary to other published studies we found no effect of such treatment on microtubule self-assembly behavior. Cleavage of isolated MAP-2 by the HIV enzyme at high salt concentrations, followed by desalting and addition of tubulin, also resulted in microtubule assembly, albeit with slightly reduced efficiency.

Demonstration of local protein synthesis within dendrites using a new cell culture system that permits the isolation of living axons and dendrites from their cell bodies

The presence of polyribosomes within dendrites suggests a capability for local dendritic protein synthesis. However, local synthesis is difficult to evaluate because of rapid somatodendritic protein transport. The present study describes a two-surfaced culture system that allowed the separation of living axons and dendrites from their cell bodies of origin. Because this system eliminates the transport of proteins produced in the cell body, it was possible to study the extent of dendritic protein synthesis directly. Hippocampal neurons were plated on a Nucleopore polycarbonate membrane that was mounted on a thick matrix of proteins (Matrigel) fixed on a coverslip. As the neurons grew, axons and dendrites grew through the membrane into the Matrigel. To evaluate local protein synthesis within dendrites, the membrane with the cell bodies was removed, leaving a dense array of transected dendrites and axons on the coverslip with few contaminant cell bodies. Absence of cell bodies was confirmed by staining with the nuclear stain Hoechst 33258. Coverslips with isolated neurites were pulse labeled with 3H-leucine for 30 min, and fixed for autoradiography to identify sites of protein synthesis. Autoradiographic analyses revealed that isolated dendrites (immunochemically identified using antibodies against MAP2) became heavily labeled, whereas axons exhibited little if any labeling. The labeling was essentially eliminated when the neurites were pulse labeled with 3H-leucine in the presence of puromycin, whereas labeling was affected only minimally by chloramphenicol. The puromycin-sensitive incorporation of 3H-leucine in dendrites demonstrates that the polyribosomes previously described are active in protein synthesis. This system will allow a characterization of synthetic activity within isolated neurites and provide a new approach to identifying proteins that are produced within dendrites.

Selective localization of messenger RNA for cytoskeletal protein MAP2 in dendrites.

For nerve cells to develop their highly polarized form, appropriate structural molecules must be targeted to either axons or dendrites. This could be achieved by the synthesis of structural proteins in the cell body and their sorting to either axons or dendrites by specific transport mechanisms. For dendrites, an alternative possibility is that proteins could be synthesized locally in the dendritic cytoplasm. This is an attractive idea because it would allow regulation of the production of structural molecules in response to local demand during dendritic development. The feasibility of dendritic protein synthesis is suggested both by the existence of dendritic polyribosomes and by the recent demonstration that newly synthesized RNA is transported into the dendrites of neurons differentiating in culture. However, to date there has been no demonstration of the selective synthesis of an identified dendrite-specific protein in the dendritic cytoplasm. Here, we use in situ hybridization with specific complementary DNA probes to show that messenger RNA for the dendrite-specific microtubule-associated protein MAP2 (refs 3-5) is present in dendrites in the developing brain. By contrast the mRNA for tubulin, a protein present in both axons and dendrites is located exclusively in neuronal cell bodies.

Lesions of entorhinal cortex produce a calpain-mediated degradation of brain spectrin in dentate gyrus. II. Anatomical studies

Lesions of the various afferents to the hippocampus have been widely used to investigate the mechanisms underlying growth and degeneration in adult mammalian CNS. It has been proposed that disturbances in intracellular calcium and activation of calcium-dependent proteases represent key steps in producing some of the consequences of the lesions. In this study, we show that lesions of the entorhinal cortex or of the commissural pathway result in profound changes in the distribution of brain spectrin. At 2 days after lesions of the entorhinal cortex, immunoreactivity to spectrin is markedly increased in the outer molecular layer (OML) of the dentate gyrus; conversely at 2 days after commissural lesions, immunoreactivity to the same antigen is increased in the inner molecular layer. The increase in immunoreactivity to spectrin varies with survival time after lesions of the entorhinal cortex. By 24 h post lesion, the increase is homogeneous across the OML, and becomes more intense by 48 h. Between 1 and 3 weeks the increase is much less than at 48 h and is concentrated at the inner border of the OML. Pretreatment of the animal with the calpain inhibitor leupeptin reduces the increase in spectrin immunoreactivity normally seen 48 h after the lesion of the entorhinal cortex. Changes in the pattern of immunoreactivity to GFAP are very different to that seen with spectrin antibodies and are consistent with the known modifications in astrocytes that follow lesions of hippocampal afferents. The results are in good agreement with the biochemical data (Seubert et al., 1988) and indicate that denervation of hippocampus results in a spatially restricted increase in the breakdown and synthesis of cytoskeletal proteins into deafferented dendrites soon after the lesion. The results also indicate that the activation of calpain appears to be necessary for some but not all the anatomical modifications that accompany lesions of the entorhinal cortex. In particular, while calpain activation might be required for the increased synthesis of cytoskeletal proteins in denervated dendrites it does not participate in astrocyte hypertrophy.

Synthesis and transport of newly formed proteins in dendrites of rat hippocampal pyramid cells. An electron microscope autoradiographic study

The synthesis and transport of newly synthesized proteins in dendrites of rat hippocampal pyramid cells were investigated. Labelled leucine was injected into the left lateral ventricle and the hippocampal region was processed for light and electron microscopic autoradiography. To differentiate between the silver grains originating from ‘sedentary’ or ‘migratory’ proteins, the radioactivity in dendritic areas free of ribosomes and rich in ribosomes was determined separately. Several conclusions were reached. (1) Protein synthesis in dendrites takes place mainly in the proximal parts although a slight synthetic activity can be observed along the whole dendritic tree as well. (2) Newly synthesized proteins are transported toward the distal dendritic region; the data obtained suggest that cisterns of the smooth endoplasmic reticulum and the microtubular system may be involved in this transport. (3) Two phases of dendritic transport may be distinguished; a fast phase with a rate of 100–200 mm/day and a slow phase with a rate of 2.8–10 mm/day. It also seems probable that the majority of the proteins newly synthesized in dendrites are transported by the slow phase.

The subunit structure of haptoglobins

Synaptic activity is a spatially limited process that requires a precise, yet dynamic, complement of proteins within the synaptic micro-domain. The maintenance and regulation of these synaptic proteins is regulated, in part, by local mRNA translation in dendrites. Protein synthesis within the postsynaptic compartment allows neurons tight spatial and temporal control of synaptic protein expression, which is critical for proper functioning of synapses and neural circuits. In this review, we discuss the identity of proteins synthesized within dendrites, the receptor-mediated mechanisms regulating their synthesis, and the possible roles for these locally synthesized proteins. We also explore how our current understanding of dendritic protein synthesis in the hippocampus can be applied to new brain regions and to understanding the pathological mechanisms underlying varied neurological diseases.