CLSTN1

This gene is a member of the calsyntenin family, a subset of the cadherin superfamily. The encoded transmembrane protein, also known as alcadein-alpha, is thought to bind to kinesin-1 motors to mediate the axonal anterograde transport of certain types of vesicle. Amyloid precursor protein (APP) is trafficked via these vesicles and so this protein is being investigated to see how it might contribute to the mechanisms underlying Alzheimer's disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2014]

Full Name

Calsyntenin 1

Function

Induces KLC1 association with vesicles and functions as a cargo in axonal anterograde transport. Complex formation with APBA2 and APP, stabilizes APP metabolism and enhances APBA2-mediated suppression of beta-APP40 secretion, due to the retardation of intracellular APP maturation. In complex with APBA2 and C99, a C-terminal APP fragment, abolishes C99 interaction with PSEN1 and thus APP C99 cleavage by gamma-secretase, most probably through stabilization of the direct interaction between APBA2 and APP. The intracellular fragment AlcICD suppresses APBB1-dependent transactivation stimulated by APP C-terminal intracellular fragment (AICD), most probably by competing with AICD for APBB1-binding. May modulate calcium-mediated postsynaptic signals (By similarity).

Biological Process

Cell adhesion Source: UniProtKB
Homophilic cell adhesion via plasma membrane adhesion molecules Source: InterPro
Neurotransmitter receptor transport to postsynaptic membrane Source: Ensembl
Positive regulation of synapse assembly Source: GO_Central
Positive regulation of synaptic transmission Source: GO_Central
Regulation of cell growth Source: Ensembl
Regulation of synapse maturation Source: Ensembl
Vesicle-mediated transport in synapse Source: Ensembl

Cellular Location

Golgi apparatus membrane; Postsynaptic cell membrane; Endoplasmic reticulum membrane; Nucleus; Neuron projection. Neurite tips. Localized in the postsynaptic membrane of both excitatory and inhibitory synapses (By similarity). The AlcICD fragment is translocated to the nucleus upon interaction with APBB1.

Topology

Extracellular: 29-859
Helical: 860-880
Cytoplasmic: 881-981

PTM

Proteolytically processed under normal cellular conditions. A primary zeta-cleavage generates a large extracellular (soluble) N-terminal domain (sAlc) and a short C-terminal transmembrane fragment (CTF1). A secondary cleavage catalyzed by presenilin gamma-secretase within the transmembrane domain releases the beta-Alc-alpha chain in the extracellular milieu and produces an intracellular fragment (AlcICD). This processing is strongly suppressed in the tripartite complex formed with APBA2 and APP, which seems to prevent the association with PSEN1.