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The Journal of Neuroscience, April 1, 2003, 23(7):2815

TUC-4b, a Novel TUC Family Variant, Regulates Neurite Outgrowth and Associates with Vesicles in the Growth Cone

Christopher C. Quinn¹, Esteban Chen¹, Tashi G. Kinjo¹, Gail Kelly¹, Alexander W. Bell², Robert C. Elliott³, Peter S. McPherson^{2, 4}, and Susan Hockfield¹

¹ Section of Neurobiology, Yale University School of Medicine, New Haven, Connecticut 06510, ² Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec H3A 2B2, Canada, ³ Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, and ⁴ Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec H3A 2B4, Canada

The TUC (TOAD-64/Ulip/CRMP) proteins are homologs of UNC-33, a protein that is required for axon extension and guidance in Caenorhabditis elegans. The TUC proteins are expressed in newly born neurons in the developing nervous system and have been implicated in semaphorin signaling and neuronal polarity. Here, we identify several new variants of the TUC family, each of which is expressed during distinct periods of neural development. We cloned and characterized TUC-4b, a variant of TUC-4a that includes a unique N-terminal extension. The functional relevance of this N-terminal domain is demonstrated by the finding that overexpression of TUC-4b, but not TUC-4a, results in increased neurite length and branching. Furthermore, whereas TUC-4a is expressed throughout life, TUC-4b is expressed exclusively during embryonic development. TUC-4b is localized to SV2 (synaptic vesicle protein 2)-positive vesicles in the central domain of the growth cone, suggesting a potential role in growth cone vesicle transport. Furthermore, TUC-4b interacts with the SH3A (Src homology 3A) domain of intersectin, an endocytic-exocytic adaptor protein. Together, these data suggest that TUC-4b can regulate neurite extension and branching through a mechanism that may involve membrane transport in the growth cone.

Key words: growth cones; neurite outgrowth; growth cone vesicles; intersectin; CRMP; Ulip; TUC; unc-33

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Copyright © 2003 Society for Neuroscience  0270-6474/03/2372815-09$05.00/0

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