Regulation of Exocytosis by Complexin

Abstract

AbbreviationsAMPA: α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; Cpx: Complexin (also known as Synaphin); GST: glutathione S-transferase; IGF-1: insulin-like growth factor-1; KD: knock-down; KO: knock-out; LTP: long-term potentiation; SNAP-23 or -25: synaptosomal-associated protein 23 or 25; SNARE: soluble N-ethylmaleimide-sensitive factor attachment protein receptor; SNARE complex: a ternary complex composed of Syntaxin, Synaptobrevin, and either SNAP-23 or SNAP-25; Syb2: Synaptobrevin 2 (also known as vesicle-associated membrane protein 2, VAMP2); Syt1: Synaptotagmin 1; Syt10: Synaptotagmin 10; WT: wild-type. INTRODUCTION Ca2+ -triggered exocytosis is an essential cellular process that mediates transmitter release to the extracellular space for intercellular communications particularly in neurons [1][2][3] . The same or similar processes are used for intracellular trafficking to deliver membrane patches or proteins to the plasma membrane [4,5] . Stimulations of neurons cause an increase in cytosolic Ca 2+ concentrations and trigger fusions of synaptic vesicles into the plasma membrane to release transmitters to the extracellular space [1][2][3] . Synaptotagmin 1 -dependent manner [6,7] . Synaptobrevin 2 (Syb2; also known as vesicle-associated membrane protein 2, VAMP2), a vesicular SNARE protein, forms a ternary SNARE complex with Syntaxin and SNAP-25 that are located in the target plasma membrane [8] . ABSTRACTComplexin (Cpx), which is expressed mainly in the nervous system, binds efficiently to the SNARE complex that is composed of either Syntaxin 1 or Syntaxin 3. Both Syntaxin 1 and Syntaxin 3 are involved in mediating synchronous neurotransmitter release in the nervous system. Cpx stabilizes the SNARE complex upon binding, and potentiates the efficacy of synchronous exocytotic process. Cpx is consisted of N-terminal, accessory α-helix, central α-helix, and C-terminal domains. Each domain of Cpx has a distinct function that is differentially involved in the regulation of priming, clamping, and activating in the exocytotic process. These functions of Cpx domains coordinately potentiate the efficacy of synchronous exocytotic process.

Dysregulation of Norepinephrine Release in the Absence of Functional Synaptotagmin 7

“…The other possible mechanism of the upregulated expression of NET in the plasma membrane is by interaction of the N‐terminus of NET with Syntaxin [Sung et al, ; Sung and Blakely, ]. Syntaxin is involved in the formation of SNARE complexes that mediate exocytosis [Südhof, , ; Rizo and Rosenmund, ; Shin, , ]. Lack of functional Syt7 may impair the formation of SNARE complexes [Hu et al, ] and lead to the accumulation of monomeric Syntaxin.…”