QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Vol. 14, Issue 8, 3356-3365, August 2003

This Article Full Text Full Text (PDF) All Versions of this Article: E02-12-0800v1 14/8/3356    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gindhart, J. G. Articles by Nandlestadt, A. Search for Related Content PubMed PubMed Citation Articles by Gindhart, J. G. Articles by Nandlestadt, A.

The Kinesin-associated Protein UNC-76 Is Required for Axonal Transport in the Drosophila Nervous System

Joseph G. Gindhart ^* , Jinyun Chen ^*, Melissa Faulkner ^*, Rita Gandhi , Karl Doerner, Tiffany Wisniewski ^* , and Aline Nandlestadt ^*

^* Biology Department, University of Massachusetts, Boston, Massachusetts 02125; Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester, Massachusetts 01655

Submitted December 9, 2002; Revised March 31, 2003; Accepted March 31, 2003
Monitoring Editor: J. Richard McIntosh

Kinesin-I is essential for the transport of membrane-bound organelles in neural and nonneural cells. However, the means by which kinesin interacts with its intracellular cargoes, and the means by which kinesin–cargo interactions are regulated in response to cellular transport requirements are not fully understood. The C terminus of the Drosophila kinesin heavy chain (KHC) was used in a two-hybrid screen of a Drosophila cDNA library to identify proteins that bind specifically to the kinesin tail domain. UNC-76 is an evolutionarily conserved cytosolic protein that binds to the tail domain of KHC in two-hybrid and copurification assays, indicating that kinesin and UNC-76 form a stable complex in vivo. Loss of Drosophila Unc-76 function results in locomotion and axonal transport defects reminiscent of the phenotypes observed in kinesin mutants, suggesting that UNC-76 is required for kinesin-dependent axonal transport. Unc-76 exhibits dosage-sensitive genetic relationships with Khc and Kinesin light chain mutations, further supporting the hypothesis that UNC-76 and kinesin-I work in a common transport pathway. Given the interaction of FEZ1, the mammalian homolog of UNC-76, with protein kinase C, and the role of FEZ1 in axon outgrowth, we propose that UNC-76 helps integrate kinesin activity in response to transport requirements in axons.

Present address: AstraZeneca R&D Boston, 35 Gatehouse Dr., Waltham, MA 02451.

Corresponding author. E-mail address: joseph.gindhart{at}umb.edu.

This article has been cited by other articles:

				N. Sakae, N. Yamasaki, K. Kitaichi, T. Fukuda, M. Yamada, H. Yoshikawa, T. Hiranita, Y. Tatsumi, J.-i. Kira, T. Yamamoto, et al. Mice lacking the schizophrenia-associated protein FEZ1 manifest hyperactivity and enhanced responsiveness to psychostimulants Hum. Mol. Genet., October 15, 2008; 17(20): 3191 - 3203. [Abstract] [Full Text] [PDF]

				N. Hirokawa and Y. Noda Intracellular Transport and Kinesin Superfamily Proteins, KIFs: Structure, Function, and Dynamics Physiol Rev, July 1, 2008; 88(3): 1089 - 1118. [Abstract] [Full Text] [PDF]

				D. D. Hackney Jump-starting kinesin J. Cell Biol., January 1, 2007; 176(1): 7 - 9. [Abstract] [Full Text] [PDF]

				T. L. Blasius, D. Cai, G. T. Jih, C. P. Toret, and K. J. Verhey Two binding partners cooperate to activate the molecular motor Kinesin-1 J. Cell Biol., January 1, 2007; 176(1): 11 - 17. [Abstract] [Full Text] [PDF]

				E. M. Assmann, M. R. Alborghetti, M. E. R. Camargo, and J. Kobarg FEZ1 Dimerization and Interaction with Transcription Regulatory Proteins Involves Its Coiled-coil Region J. Biol. Chem., April 14, 2006; 281(15): 9869 - 9881. [Abstract] [Full Text] [PDF]

				J. G. Gindhart Towards an understanding of kinesin-1 dependent transport pathways through the study of protein-protein interactions Brief Funct Genomic Proteomic, March 1, 2006; 5(1): 74 - 86. [Abstract] [Full Text] [PDF]

				S. Pagliardini, J. Ren, R. Wevrick, and J. J. Greer Developmental Abnormalities of Neuronal Structure and Function in Prenatal Mice Lacking the Prader-Willi Syndrome Gene Necdin Am. J. Pathol., July 1, 2005; 167(1): 175 - 191. [Abstract] [Full Text] [PDF]

				T. Suzuki, Y. Okada, S. Semba, Y. Orba, S. Yamanouchi, S. Endo, S. Tanaka, T. Fujita, S. Kuroda, K. Nagashima, et al. Identification of FEZ1 as a Protein That Interacts with JC Virus Agnoprotein and Microtubules: ROLE OF AGNOPROTEIN-INDUCED DISSOCIATION OF FEZ1 FROM MICROTUBULES IN VIRAL PROPAGATION J. Biol. Chem., July 1, 2005; 280(26): 24948 - 24956. [Abstract] [Full Text] [PDF]

				M. H. Naghavi, T. Hatziioannou, G. Gao, and S. P. Goff Overexpression of fasciculation and elongation protein {zeta}-1 (FEZ1) induces a post-entry block to retroviruses in cultured cells Genes & Dev., May 1, 2005; 19(9): 1105 - 1115. [Abstract] [Full Text] [PDF]

				S. Lee, C. L. Walker, B. Karten, S. L. Kuny, A. A. Tennese, M. A. O'Neill, and R. Wevrick Essential role for the Prader-Willi syndrome protein necdin in axonal outgrowth Hum. Mol. Genet., March 1, 2005; 14(5): 627 - 637. [Abstract] [Full Text] [PDF]

				F. Okumura, S. Hatakeyama, M. Matsumoto, T. Kamura, and K. I. Nakayama Functional Regulation of FEZ1 by the U-box-type Ubiquitin Ligase E4B Contributes to Neuritogenesis J. Biol. Chem., December 17, 2004; 279(51): 53533 - 53543. [Abstract] [Full Text] [PDF]

				S. P. Koushika, A. M. Schaefer, R. Vincent, J. H. Willis, B. Bowerman, and M. L. Nonet Mutations in Caenorhabditis elegans Cytoplasmic Dynein Components Reveal Specificity of Neuronal Retrograde Cargo J. Neurosci., April 21, 2004; 24(16): 3907 - 3916. [Abstract] [Full Text] [PDF]