Role Of MAP1B Research Articles

The role of Map1b in regulating osteoblast polarity, proliferation, differentiation and migration

Osteoblast polarity, proliferation, differentiation, and migration are essential for maintaining normal bone structure and function. While the microtubule-associated protein Map1b has been extensively studied in nerve cells, its role in bone cells is less known. We investigated the functional significance of Map1b in mouse bone marrow stromal cells (ST2) and elucidated its relationship and influence on cytoskeletal polarity and Golgi organization. Our results suggest that Map1b, as a microtubule regulatory protein, can also regulate the expression of cyclin PCNA, p-H3(S10) and migration-related protein integrin β1, thereby affecting the proliferation and migration of osteoblasts. The downstream target gene Rgc32 was screened by RNA sequencing. Furthermore, Map1b, as a downstream mediator, regulates the Wnt5a signaling pathway. This study expands our understanding of the involvement of Map1b in bone biology and highlights its crucial role in governing osteoblast polarity, proliferation, and migration, thereby providing a basis for developing novel therapeutic strategies targeting Map1b in orthopedic medicine and promoting precision treatment modalities. Further investigations on the precise mechanisms underlying Map1b's influence on bone cell function and disease progression are needed.

The MAP1B Binding Domain of Nav1.6 Is Required for Stable Expression at the Axon Initial Segment.

Nav1.6 (SCN8A) is a major voltage-gated sodium channel in the mammalian CNS, and is highly concentrated at the axon initial segment (AIS). As previously demonstrated, the microtubule associated protein MAP1B binds the cytoplasmic N terminus of Nav1.6, and this interaction is disrupted by the mutation p.VAVP(77-80)AAAA. We now demonstrate that this mutation results in WT expression levels on the somatic surface but reduced surface expression at the AIS of cultured rat embryonic hippocampal neurons from both sexes. The mutation of the MAP1B binding domain did not impair vesicular trafficking and preferential delivery of Nav1.6 to the AIS; nor was the diffusion of AIS inserted channels altered relative to WT. However, the reduced AIS surface expression of the MAP1B mutant was restored to WT levels by inhibiting endocytosis with Dynasore, indicating that compartment-specific endocytosis was responsible for the lack of AIS accumulation. Interestingly, the lack of AIS targeting resulted in an elevated percentage of persistent current, suggesting that this late current originates predominantly in the soma. No differences in the voltage dependence of activation or inactivation were detected in the MAP1B binding mutant relative to WT channel. We hypothesize that MAP1B binding to the WT Nav1.6 masks an endocytic motif, thus allowing long-term stability on the AIS surface. This work identifies a critical and important new role for MAP1B in the regulation of neuronal excitability and adds to our understanding of AIS maintenance and plasticity, in addition to identifying new target residues for pathogenic mutations of SCN8ASIGNIFICANCE STATEMENT Nav1.6 is a major voltage-gated sodium channel in human brain, where it regulates neuronal activity due to its localization at the axon initial segment (AIS). Nav1.6 mutations cause epilepsy, intellectual disability, and movement disorders. In the present work, we show that loss of interaction with MAP1B within the Nav1.6 N terminus reduces the steady-state abundance of Nav1.6 at the AIS. The effect is due to increased Nav1.6 endocytosis at this neuronal compartment rather than a failure of forward trafficking to the AIS. This work confirms a new biological role of MAP1B in the regulation of sodium channel localization and will contribute to future analysis of patient mutations in the cytoplasmic N terminus of Nav1.6.

Role of MAP1B in axonal retrograde transport of mitochondria

The MAPs (microtubule-associated proteins) MAP1B and tau are well known for binding to microtubules and stabilizing these structures. An additional role for MAPs has emerged recently where they appear to participate in the regulation of transport of cargos on the microtubules found in axons. In this role, tau has been associated with the regulation of anterograde axonal transport. We now report that MAP1B is associated with the regulation of retrograde axonal transport of mitochondria. This finding potentially provides precise control of axonal transport by MAPs at several levels: controlling the anterograde or retrograde direction of transport depending on the type of MAP involved, controlling the speed of transport and controlling the stability of the microtubule tracks upon which transport occurs.

A role of MAP1B in Reelin-dependent Neuronal Migration

The signaling cascades governing neuronal migration are believed to link extracellular signals to cytoskeletal components. MAP1B is a neuron-specific microtubule-associated protein implicated in the control of the dynamic stability of microtubules and in the cross-talk between microtubules and actin filaments. Here we show that Reelin can induce mode I MAP1B phosphorylation, both in vivo and in vitro, through gsk3 and cdk5 activation. Additionally, mDab1 participates in the signaling cascade responsible for mode I MAP1B phosphorylation. Conversely, MAP1B-deficient mice display an abnormal structuring of the nervous system, especially in brain laminated areas, indicating a failure in neuronal migration. Therefore, we propose that Reelin can induce post-translational modifications on MAP1B that could correlate with its function in neuronal migration.

Quantitation of microtubule-associated protein MAP-1B in brain and other tissues

1. 1. The presence of micro tubule-associated protein MAP-1B in all mammalian tissues tested, as well as in brain, has been demonstrated by immunoblotting using a monospecific polyclonal antibody. 2. 2. The expression of brain MAP-1B is developmentally controlled, as it is less abundant in adult than in newborn rat brain, where it is a major microtubule assembly promoting factor. 3. 3. The level of MAP-1B in tissues other than brain is lower than it is in brain; but the relative ratios of MAP-1B to tubulin are very similar in all tissues, thus differring from the observed for MAP-2 or tau. 4. 4. The amount of MAP-1B in non-nervous tissues seems not to be under developmental control. 5. 5. These results are consistent with a role for MAP-1B in the assembly of microtubules in most cells.