Abstract
Amyloid precursor protein (APP) is a transmembrane protein highly expressed in neurons. The full-length protein has cell-adhesion and receptor-like properties, which play roles in synapse formation and stability. Furthermore, APP can be cleaved by several proteases into numerous fragments, many of which affect synaptic function and stability. This review article focuses on the mechanisms of APP in structural spine plasticity, which encompasses the morphological alterations at excitatory synapses. These occur as changes in the number and morphology of dendritic spines, which correspond to the postsynaptic compartment of excitatory synapses. Both overexpression and knockout (KO) of APP lead to impaired synaptic plasticity. Recent data also suggest a role of APP in the regulation of astrocytic D-serine homeostasis, which in turn regulates synaptic plasticity.
Highlights
Structural synaptic plasticity refers to morphologically observable changes of synapses which accompany the classical electrophysiological events during synaptic plasticity
Synaptogenesis and neurite outgrowth may be mediated by full-length Amyloid precursor protein (APP), which has been shown to exhibit cell adhesion- and receptor-like properties (Qiu et al, 1995; Ando et al, 1999; Turner et al, 2003; Soba et al, 2005; Müller and Zheng, 2012; Coburger et al, 2014; Deyts et al, 2016): there is convincing evidence that two distinct extracellular E1 domains from neighboring molecules of APP, APLP1 and APLP2 (Soba et al, 2005; Baumkötter et al, 2012; Deyts et al, 2016) can interact via their heparin binding domains (HBDs), and form a so-called heparin cross-linked dimer (Coburger et al, 2014)
We recently studied dendritic spines of layer V pyramidal neurons of the somatosensory cortex in 4 month old APP-KO × GFP-M mice (Zou et al, 2016), which is accessible to chronic in vivo imaging
Summary
Amyloid precursor protein (APP) is a transmembrane protein highly expressed in neurons. APP can be cleaved by several proteases into numerous fragments, many of which affect synaptic function and stability. This review article focuses on the mechanisms of APP in structural spine plasticity, which encompasses the morphological alterations at excitatory synapses. These occur as changes in the number and morphology of dendritic spines, which correspond to the postsynaptic compartment of excitatory synapses. Both overexpression and knockout (KO) of APP lead to impaired synaptic plasticity. Recent data suggest a role of APP in the regulation of astrocytic D-serine homeostasis, which in turn regulates synaptic plasticity.
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