Disease relevance of CPLX1

• These alterations in complexin levels may also play an important role in neuronal cell loss following TBI, and thus contribute to the pathophysiology of cerebral damage following brain injury [1].

Psychiatry related information on CPLX1

• Hippocampal synaptic pathology in schizophrenia, bipolar disorder and major depression: a study of complexin mRNAs [2].

High impact information on CPLX1

• Here we propose that complexin binding activates SNARE complexes into a metastable state and that Ca(2+) binding to synaptotagmin 1 triggers fast exocytosis by displacing complexin from metastable SNARE complexes [3].
• Specifically, we demonstrate that, biochemically, synaptotagmin 1 competes with complexin for SNARE-complex binding, thereby dislodging complexin from SNARE complexes in a Ca(2+)-dependent manner [3].
• In the recently solved crystal structure of complexin I bound to the synaptic SNARE complex, complexin binds along the groove between the syntaxin and synaptobrevin coils [4].
• This structure, together with NMR data, suggests that the role of complexin is to stabilize the SNARE complex as it forms from SNAREs in vesicle and target membranes [4].
• OBJECTIVES: To determine the amount and distribution of complexin proteins in the hippocampus of subjects with schizophrenia, in parallel with markers for excitatory and inhibitory nerve terminals [5].

Chemical compound and disease context of CPLX1

• Early, transient increase in complexin I and complexin II in the cerebral cortex following traumatic brain injury is attenuated by N-acetylcysteine [1].

Biological context of CPLX1

• The cpx1 and cpx2 genes of maize are a singular example of duplicated genes that have diverged by deletion and creation of protein targeting information [6].
• Physiologically, increasing the local concentration of complexin selectively impairs fast Ca(2+)-triggered exocytosis but retains other forms of SNARE-dependent fusion [3].
• Accordingly, Ca(2+) may initiate membrane fusion by acting directly or indirectly on complexin, thus allowing the conformational transitions of the trans SNARE complex that are thought to drive membrane fusion [7].
• Although there are structural differences in the active site clefts of CF1, CF2, and CPLX, a number of complex-stabilizing interactions are conserved [8].
• Therefore, the transient up-regulation pattern of CPX-1 expression may be important for the successful progression from pre-osteoclasts to mature osteoclasts [9].

Anatomical context of CPLX1

• Altered immunoreactivity of complexin protein in prefrontal cortex in severe mental illness [10].
• In the hippocampus, levels of complexin II, synaptobrevin 2, rab3A, and also of alpha-SNAP, were markedly elevated in HD brains [11].
• GFP fused with CPX1 localized to the plastids [6].
• Transient increases in the levels of complexin I and complexin II proteins were detected in the injured cerebral cortex 6 h following TBI [1].
• A complexin/synaptotagmin 1 switch controls fast synaptic vesicle exocytosis [3].

Associations of CPLX1 with chemical compounds

• DESIGN: We used immunocytochemistry to study complexin I and complexin II proteins in hippocampus, as well as the vesicular transporters for gamma-aminobutyric acid (GABA) and for glutamate [5].
• Disturbances in the complexin proteins in subjects with schizophrenia were greater than those observed for vesicular gamma-aminobutyric acid or vesicular glutamate transporters [5].
• Treatment of rats with antipsychotic drugs or with the psychotomimetic drugs amphetamine or ketamine did not alter the complexin II-complexin I ratio [5].
• Treatment of rats with antipsychotics (haloperidol or chlorpromazine) for 2 weeks had no effect on hippocampal cx mRNAs [2].
• The amino terminus (Leu 102 to Gly 105) of CF1 and CF2 molecules A and B differs from the conformation found in CPLX by bending away from the molecule and interacting with the active site cleft of symmetry-related molecules [8].

Physical interactions of CPLX1

• The cytosolic protein synaphin/complexin critically regulates fast neurotransmitter release at the synapse by binding to SNARE complex [12].

Other interactions of CPLX1

• Ten and eleven haplotype-tagging (ht)SNPs in CPLX1 and CPLX2, respectively, were selected [13].
• Synaptophysin, complexin II and GAP-43 were reduced in bipolar disorder [14].
• In schizophrenia, VGLUT1 mRNA was decreased in hippocampal formation and DPFC, complexin II mRNA was reduced in DPFC and STC, and complexin I mRNA decreased in STC [15].
• Sema3A also correlated negatively with synaptophysin and complexin II mRNAs [16].

Analytical, diagnostic and therapeutic context of CPLX1

• We investigated the presynaptic proteins complexin (Cx) I and Cx II in postmortem prefrontal cortex in schizophrenia (n = 13; six suicide, seven nonsuicide), major depression (n= 11, all suicide) and controls (n = 11) with an enzyme-linked immunoadsorbent assay (ELISA) [10].

References