Novel dendritic kinesin sorting identified by different process targeting of two related kinesins: KIF21A and KIF21B.
Neurons use kinesin and dynein microtubule-dependent motor proteins to transport essential cellular components along axonal and dendritic microtubules. In a search for new kinesin-like proteins, we identified two neuronally enriched mouse kinesins that provide insight into a unique intracellular kinesin targeting mechanism in neurons. KIF21A and KIF21B share colinear amino acid similarity to each other, but not to any previously identified kinesins outside of the motor domain. Each protein also contains a domain of seven WD-40 repeats, which may be involved in binding to cargoes. Despite the amino acid sequence similarity between KIF21A and KIF21B, these proteins localize differently to dendrites and axons. KIF21A protein is localized throughout neurons, while KIF21B protein is highly enriched in dendrites. The plus end-directed motor activity of KIF21B and its enrichment in dendrites indicate that models suggesting that minus end-directed motor activity is sufficient for dendrite specific motor localization are inadequate. We suggest that a novel kinesin sorting mechanism is used by neurons to localize KIF21B protein to dendrites since its mRNA is restricted to the cell body.
Marszalek
J R
JR
Biomedical Sciences Graduate Program, Division of Cellular and Molecular Medicine, Department of Pharmacology, University of California San Diego, La Jolla, California 92093-0683, USA.
Weiner
J A
JA
Farlow
S J
SJ
Chun
J
J
Goldstein
L S
LS
D000818:Animals; D000906:Antibodies; D002874:Chromosome Mapping; D003712:Dendrites / Q000201:enzymology*; D017403:In Situ Hybridization; D007527:Isoenzymes / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016547:Kinesins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D020409:Molecular Motor Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D009474:Neurons / Q000201:enzymology / Q000648:ultrastructure; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D012091:Repetitive Sequences, Nucleic Acid; D017386:Sequence Homology, Amino Acid
D000906:Antibodies; D007527:Isoenzymes; C485598:Kif21a protein, mouse; C119024:Kif21b protein, mouse; D020409:Molecular Motor Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D016547:Kinesins