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© The Rockefeller University Press, 0021-9525/1999//1277 $5.00
The Journal of Cell Biology, Volume 146, Number 6, , 1999 1277-1288

Defective Kinesin Heavy Chain Behavior in Mouse Kinesin Light Chain Mutants

^a Howard Hughes Medical Institute, Department of Cellular and Molecular Medicine, Department of Pharmacology and Program in Biomedical Sciences, School of Medicine, University of California San Diego, La Jolla, California 92093-0683
HHMI/CMM Room 334, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0683.(858) 534-9701(858) 534-9702

lgoldstein{at}ucsd.edu

Conventional kinesin, kinesin-I, is a heterotetramer of two kinesin heavy chain (KHC) subunits (KIF5A, KIF5B, or KIF5C) and two kinesin light chain (KLC) subunits. While KHC contains the motor activity, the role of KLC remains unknown. It has been suggested that KLC is involved in either modulation of KHC activity or in cargo binding. Previously, we characterized KLC genes in mouse (Rahman, A., D.S. Friedman, and L.S. Goldstein. 1998. J. Biol. Chem. 273:15395–15403). Of the two characterized gene products, KLC1 was predominant in neuronal tissues, whereas KLC2 showed a more ubiquitous pattern of expression. To define the in vivo role of KLC, we generated KLC1 gene-targeted mice. Removal of functional KLC1 resulted in significantly smaller mutant mice that also exhibited pronounced motor disabilities. Biochemical analyses demonstrated that KLC1 mutant mice have a pool of KIF5A not associated with any known KLC subunit. Immunofluorescence studies of sensory and motor neuron cell bodies in KLC1 mutants revealed that KIF5A colocalized aberrantly with the peripheral cis-Golgi marker giantin in mutant cells. Striking changes and aberrant colocalization were also observed in the intracellular distribution of KIF5B and β'-COP, a component of COP1 coatomer. Taken together, these data best support models that suggest that KLC1 is essential for proper KHC activation or targeting.

Key Words: kinesin • kinesin light chain • Golgi apparatus • intracellular trafficking • gene targeting

© 1999 The Rockefeller University Press

Amena Rahman's current address is Canji Inc., 3525 John Hopkins Court, San Diego, CA 92121.

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