The septin CDCrel-1 is dispensable for normal development and neurotransmitter release.
Septins are GTPases required for the completion of cytokinesis in a variety of organisms, yet their role in this process is not known. Septins may have additional functions since the mammalian septin CDCrel-1 is predominantly expressed in the nervous system, a largely postmitotic tissue. While relatively little is known about the function of this protein, we have previously shown that it is involved in regulated secretion. In addition, the gene encoding this protein maps to a locus often deleted in velo-cardiofacial and DiGeorge syndromes, and CDCrel-1 has recently been shown to be a direct target of the E3 ubiquitin ligase activity of Parkin, a causative agent in autosomal recessive forms of Parkinson's disease. Here we show that CDCrel-1 expression rises at the time of synaptic maturation and that CDCrel-1 is present in a complex that includes the septins Nedd5 and CDC10. To investigate its function in the nervous system, we generated homozygotic CDCrel-1 null mice and showed that these mice appear normal with respect to synaptic properties and hippocampal neuron growth in vitro. Moreover, we found that while the expression of a number of synaptic proteins is not affected in the CDCrel-1 mutant mice, the expression of other septins is altered. Together, these data suggest that CDCrel-1 is not essential for neuronal development or function, and that changes in expression of other septins may account for its functional redundancy.
Peng
Xiao-Rong
XR
Programmes in Cell Biology. Brain and Behavior, Hospital for Sick Children, Toronto, Ontario, Canada.
Jia
Zhengping
Z
Zhang
Yu
Y
Ware
Jerry
J
Trimble
William S
WS
D000818:Animals; D001923:Brain Chemistry; D018797:Cell Cycle Proteins / Q000378:metabolism; D002458:Cell Fractionation; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005260:Female; D020558:GTP Phosphohydrolases / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006624:Hippocampus / Q000166:cytology / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D046911:Macromolecular Substances; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D011995:Recombination, Genetic; D058112:Septins; D013569:Synapses / Q000502:physiology*; D016335:Zinc Fingers
D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D046911:Macromolecular Substances; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D020558:GTP Phosphohydrolases; C109366:SEPTIN5 protein, human; C113158:SEPTIN7 protein, human; C106863:Sept2 protein, mouse; C491612:Sept5 protein, mouse; D058112:Septins