Role of the PAR-3-KIF3 complex in the establishment of neuronal polarity.
Neurons polarize to form elaborate multiple dendrites and one long axon. The establishment and maintenance of axon/dendrite polarity are fundamentally important for neurons. Recent studies have demonstrated that the polarity complex PAR-3-PAR-6-atypical protein kinase C (aPKC) is involved in polarity determination in many tissues and cells. The function of the PAR-3-PAR-6-aPKC protein complex depends on its subcellular localization in polarized cells. PAR-3 accumulates at the tip of growing axons in cultured rat hippocampal neurons, but the molecular mechanism of this localization remains unknown. Here we identify a direct interaction between PAR-3 and KIF3A, a plus-end-directed microtubule motor protein, and show that aPKC can associate with KIF3A through its interaction with PAR-3. The expression of dominant-negative PAR-3 and KIF3A fragments that disrupt PAR-3-KIF3A binding inhibited the accumulation of PAR-3 and aPKC at the tip of the neurites and abolished neuronal polarity. These results suggest that PAR-3 is transported to the distal tip of the axon by KIF3A and that the proper localization of PAR-3 is required to establish neuronal polarity.
Nishimura
Takashi
T
Department of Cell Pharmacology, Graduate School of Medicine, Nagoya University, 65 Tsurumai, Showa, Nagoya, Aichi 466-8550, Japan.
Kato
Katsuhiro
K
Yamaguchi
Tomoya
T
Fukata
Yuko
Y
Ohno
Shigeo
S
Kaibuchi
Kozo
K
D000818:Animals; D001370:Axonal Transport / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics; D016764:Cell Polarity / Q000235:genetics*; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D005333:Fetus; D020439:Growth Cones / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D046911:Macromolecular Substances; D020409:Molecular Motor Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D011493:Protein Kinase C / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000235:genetics; D021381:Protein Transport / Q000235:genetics*; D051381:Rats
D002352:Carrier Proteins; C087415:KIF3A protein, human; C490201:Kif3a protein, rat; D046911:Macromolecular Substances; D020409:Molecular Motor Proteins; D009419:Nerve Tissue Proteins; C472451:Pard3 protein, rat; C115015:PKC-3 protein; D011493:Protein Kinase C; D016547:Kinesins