Disease relevance of Cit

• Using constitutively active and dominant negative mutants, we showed that citron kinase is involved in the morphologic differentiation of N1E-115 neuroblastoma cells induced by serum starvation [1].

High impact information on Cit

• We propose that citron kinase regulates cytokinesis at a step after Rho in the contractile process [2].
• Citron kinase localizes to the cleavage furrow and midbody of HeLa cells; Rho is also localized in the midbody [2].
• Although hVam6p exhibits homology to the Saccharomyces cerevisiae vacuolar protein sorting gene product Vam6p/Vps39p, the presence of a citron homology (CNH) domain at the NH(2) terminus is unique to the human protein [3].
• The Arg-Cit cycle appears to be the equivalent in the endothelial cell to the formation of urea by the liver [4].
• In a heterologous system, Citron was shown to form a heteromeric complex not only with PSD-95 but also with NMDA receptors [5].

Biological context of Cit

• We find that overexpression of citron mutants results in the production of multinucleate cells and that a kinase-active mutant causes abnormal contraction during cytokinesis [2].
• In addition, confocal time-lapse imaging of mitoses at the VZ surface shows that citron kinase is also necessary for phases of the cell cycle just prior to cytokinesis [6].
• We previously reported that Citron kinase knockout mice are affected by a complex neurological syndrome caused by cytokinesis block and apoptosis of specific neuronal precursors [7].
• Citron kinase is therefore an essential multifunctional regulator of cell divisions in the VZ, and may serve to coordinate chromosome segregation with cytokinesis in neuronal precursors [6].
• Role of citron kinase in dendritic morphogenesis of cortical neurons [1].

Anatomical context of Cit

• Citron kinase is a cell cycle-dependent, nuclear protein required for G2/M transition of hepatocytes [8].
• In citron kinase null mutants, a large proportion of neuronal cells within neocortex are binucleate; however, very few glial cells are binucleate [6].
• Our data indicate that Citron kinase is specifically required for cytokinesis of the male germ line [7].
• More importantly, quantitative analysis of citron kinase knockout cerebral cortex displayed that this molecule may differentially regulate the morphology of the dendritic compartment in corticocollicular versus callosally-projecting pyramidal neurons [1].
• Citron colocalization with PSD-95 occurred, not exclusively but certainly, at glutamatergic synapses in a limited set of neurons, such as the thalamic excitatory neurons; Citron expression, however, could not be detected in the principal neurons of the hippocampus and the cerebellum in the adult mouse brain [5].

Associations of Cit with chemical compounds

• Since there is no known codon for citrulline, we have constructed a mutant form of recombinant murine MBP (rmMBP) in which 5 Arg and 1 Lys residues have been replaced by Gln as the most reasonable analogue of Cit [9].

Other interactions of Cit

• Citron kinase is a myotonin-related protein acting downstream of the GTPase Rho in cytokinesis control [7].
• Citron kinase is a regulator of mitosis and neurogenic cytokinesis in the neocortical ventricular zone [6].
• The former was required for binding to citron, whereas the latter was necessary for binding to rhophilin [10].

References