Cypin regulates dendrite patterning in hippocampal neurons by promoting microtubule assembly.
Dendrite branching has an important role in normal brain function. Here we report that overexpression of cypin, a protein that has guanine deaminase activity and is expressed in developing processes in rat hippocampal neurons, results in increased dendrite branching in primary culture. Mutant cypin proteins that lack guanine deaminase activity act in a dominant-negative manner when expressed in primary neurons. Furthermore, we knocked down cypin protein levels using a new strategy: expressing a 5' end-mutated U1 small nuclear RNA (snRNA) to inhibit maturation of cypin mRNA. Neurons that express this mutant snRNA show little or no detectable cypin protein and fewer dendrites than normal. In addition, we found that cypin binds directly to tubulin heterodimers and promotes microtubule polymerization. Thus, our results demonstrate a new pathway by which dendrite patterning is regulated, and we also introduce a new method for decreasing endogenous protein expression in neurons.
Akum
Barbara F
BF
Department of Cell Biology and Neuroscience, and Molecular Biosciences Graduate Program, Rutgers University, 604 Allison Road, Piscataway, New Jersey 08854-8082, USA.
Chen
Maxine
M
Gunderson
Samuel I
SI
Riefler
Gary M
GM
Scerri-Hansen
Monica M
MM
Firestein
Bonnie L
BL
D000818:Animals; D019521:Body Patterning / Q000502:physiology*; D002352:Carrier Proteins / Q000502:physiology*; D002478:Cells, Cultured; D003712:Dendrites / Q000502:physiology*; D004622:Embryo, Mammalian; D006148:Guanine Deaminase / Q000502:physiology*; D006624:Hippocampus / Q000196:embryology*; D007150:Immunohistochemistry; D008870:Microtubules / Q000502:physiology*; D009154:Mutation; D012342:RNA, Small Nuclear / Q000235:genetics; D051381:Rats; D014162:Transfection
D002352:Carrier Proteins; D012342:RNA, Small Nuclear; C485728:Gda protein, rat; D006148:Guanine Deaminase