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Gene Review

CPLX1  -  complexin 1

Homo sapiens

Synonyms: CPX I, CPX-I, CPX1, Complexin I, Complexin-1, ...
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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


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


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


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].


  1. Early, transient increase in complexin I and complexin II in the cerebral cortex following traumatic brain injury is attenuated by N-acetylcysteine. Yi, J.H., Hoover, R., McIntosh, T.K., Hazell, A.S. J. Neurotrauma (2006) [Pubmed]
  2. Hippocampal synaptic pathology in schizophrenia, bipolar disorder and major depression: a study of complexin mRNAs. Eastwood, S.L., Harrison, P.J. Mol. Psychiatry (2000) [Pubmed]
  3. A complexin/synaptotagmin 1 switch controls fast synaptic vesicle exocytosis. Tang, J., Maximov, A., Shin, O.H., Dai, H., Rizo, J., Südhof, T.C. Cell (2006) [Pubmed]
  4. Sealed with a twist: complexin and the synaptic SNARE complex. Marz, K.E., Hanson, P.I. Trends Neurosci. (2002) [Pubmed]
  5. Hippocampal complexin proteins and cognitive dysfunction in schizophrenia. Sawada, K., Barr, A.M., Nakamura, M., Arima, K., Young, C.E., Dwork, A.J., Falkai, P., Phillips, A.G., Honer, W.G. Arch. Gen. Psychiatry (2005) [Pubmed]
  6. Divergence of duplicated genes in maize: evolution of contrasting targeting information for enzymes in the porphyrin pathway. Williams, P., Hardeman, K., Fowler, J., Rivin, C. Plant J. (2006) [Pubmed]
  7. X-ray structure of a neuronal complexin-SNARE complex from squid. Bracher, A., Kadlec, J., Betz, H., Weissenhorn, W. J. Biol. Chem. (2002) [Pubmed]
  8. Crystal structures of recombinant 19-kDa human fibroblast collagenase complexed to itself. Lovejoy, B., Hassell, A.M., Luther, M.A., Weigl, D., Jordan, S.R. Biochemistry (1994) [Pubmed]
  9. Elucidation of CPX-1 involvement in RANKL-induced osteoclastogenesis by a proteomics approach. Chang, E.J., Kwak, H.B., Kim, H., Park, J.C., Lee, Z.H., Kim, H.H. FEBS Lett. (2004) [Pubmed]
  10. Altered immunoreactivity of complexin protein in prefrontal cortex in severe mental illness. Sawada, K., Young, C.E., Barr, A.M., Longworth, K., Takahashi, S., Arango, V., Mann, J.J., Dwork, A.J., Falkai, P., Phillips, A.G., Honer, W.G. Mol. Psychiatry (2002) [Pubmed]
  11. Abnormalities in the synaptic vesicle fusion machinery in Huntington's disease. Morton, A.J., Faull, R.L., Edwardson, J.M. Brain Res. Bull. (2001) [Pubmed]
  12. Phosphorylated synaphin/complexin found in the brain exhibits enhanced SNARE complex binding. Shata, A., Saisu, H., Odani, S., Abe, T. Biochem. Biophys. Res. Commun. (2007) [Pubmed]
  13. No association of complexin1 and complexin2 genes with schizophrenia in a Japanese population. Kishi, T., Ikeda, M., Suzuki, T., Kitajima, T., Yamanouchi, Y., Kinoshita, Y., Ozaki, N., Iwata, N. Schizophr. Res. (2006) [Pubmed]
  14. Synaptic pathology in the anterior cingulate cortex in schizophrenia and mood disorders. A review and a Western blot study of synaptophysin, GAP-43 and the complexins. Eastwood, S.L., Harrison, P.J. Brain Res. Bull. (2001) [Pubmed]
  15. Decreased expression of vesicular glutamate transporter 1 and complexin II mRNAs in schizophrenia: further evidence for a synaptic pathology affecting glutamate neurons. Eastwood, S.L., Harrison, P.J. Schizophr. Res. (2005) [Pubmed]
  16. The axonal chemorepellant semaphorin 3A is increased in the cerebellum in schizophrenia and may contribute to its synaptic pathology. Eastwood, S.L., Law, A.J., Everall, I.P., Harrison, P.J. Mol. Psychiatry (2003) [Pubmed]
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