calsyntenin-1; alcadein-alpha; alc-alpha; Alzheimer-related cadherin-like protein; non-classical cadherin XB31alpha (CLSTN1, CS1, KIAA0911)
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Function
- induces KLC1 association with vesicles
- functions as cargo in axonal anterograde transport
- complex formation with APBA2 & APP
- stabilizes APP metabolism & enhances APBA2-mediated suppression of beta-APP40 secretion, due to retardation of intracellular APP maturation
- in complex with APBA2 & APP-C99 (C-terminal APP fragment), abolishes C99 interaction with PSEN1 & thus APP-C99 cleavage by gamma-secretase, likely via stabilization of the interaction between APBA2 & APP
- 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 Ca+2-mediated postsynaptic signals
- proteolytically processed under normal cellular conditions
- primary zeta-cleavage generates a large extracellular (soluble) N-terminal domain (salc) & a short C-terminal transmembrane fragment (CTF1)
- secondary cleavage catalyzed by presenilin gamma-secretase within the transmembrane domain releases the beta-alc-alpha chain in the extracellular milieu & produces an intracellular fragment (alcICD); processing is strongly suppressed in the tripartite complex formed with APBA2 & APP, which seems to prevent the association with PSEN1
- directly interacts with APBA2
- forms a tripartite complex with APBA2 & APP
- the CTF1 chain interacts with PSEN1
- the intracellular fragment alcICD interacts with APBB1;
- this interaction stabilizes alcICD metabolism
- interacts with KLC1 & APBB1 (putative)
Structure
- the cytoplasmic domain is involved in interaction with APBA2, as well as the binding of synaptic Ca+2 (putative)
- contains 2 cadherin domains
Compartment
- single-pass type 1 membrane protein
- endoplasmic reticulum membrane
- Golgi membrane
- cell projection, cell junction
- synapse, postsynaptic cell membrane
- nucleus
- neurite tips
- localized in the postsynaptic membrane of both excitatory & inhibitory synapses (putative)
- the alcICD fragment is translocated to the nucleus upon interaction with APBB1
Alternative splicing
named isoforms=2
Expression
- expressed in the brain > heart, skeletal muscle, kidney & placenta
Pathology
- accumulates in dystrophic neurites around the amyloid core of Alzheimer disease senile plaques (at protein level)