Novel Dendritic Kinesin Sorting Identified by Different Process Targeting of Two Related Kinesins: KIF21A and KIF21B

doi:10.1083/jcb.145.3.469

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J. Cell Biol., Volume 145, Number 3, May 3, 1999 469-479

Novel Dendritic Kinesin Sorting Identified by Different Process Targeting of Two Related Kinesins: KIF21A and KIF21B

Joseph R. Marszalek,^*^§ Joshua A. Weiner, Samuel J. Farlow,^§ Jerold Chun,^* and Lawrence S.B. Goldstein^*^§

^* Biomedical Sciences Graduate Program; Neurosciences Graduate Program; and ^§ Howard Hughes Medical Institute, Division of Cellular and Molecular Medicine, Department of Pharmacology, University of California San Diego, La Jolla, California 92093-0683

Neurons use kinesin and dynein microtubule-dependent motor proteins to transport essential cellular components along axonaland dendritic microtubules. In a search for new kinesin-like proteins,we identified two neuronally enriched mouse kinesins that provideinsight into a unique intracellular kinesin targeting mechanismin neurons. KIF21A and KIF21B share colinear amino acid similarityto each other, but not to any previously identified kinesins outsideof the motor domain. Each protein also contains a domain of sevenWD-40 repeats, which may be involved in binding to cargoes. Despitethe amino acid sequence similarity between KIF21A and KIF21B,these proteins localize differently to dendrites and axons. KIF21Aprotein is localized throughout neurons, while KIF21B proteinis highly enriched in dendrites. The plus end-directed motor activityof KIF21B and its enrichment in dendrites indicate that modelssuggesting that minus end-directed motor activity is sufficientfor dendrite specific motor localization are inadequate. We suggestthat a novel kinesin sorting mechanism is used by neurons to localizeKIF21B protein to dendrites since its mRNA is restricted to thecellbody.

Key words: kinesin; protein sorting; WD-40 repeats; neuron transport; dendrite

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