PMID- 16864656 OWN - NLM STAT- MEDLINE DCOM- 20060919 LR - 20211203 IS - 0021-9525 (Print) IS - 1540-8140 (Electronic) IS - 0021-9525 (Linking) VI - 174 IP - 3 DP - 2006 Jul 31 TI - Transport of PIP3 by GAKIN, a kinesin-3 family protein, regulates neuronal cell polarity. PG - 425-36 AB - Phosphatidylinositol-(3,4,5)-trisphosphate (PIP3), a product of phosphatidylinositol 3-kinase, is an important second messenger implicated in signal transduction and membrane transport. In hippocampal neurons, the accumulation of PIP3 at the tip of neurite initiates the axon specification and neuronal polarity formation. We show that guanylate kinase-associated kinesin (GAKIN), a kinesin-like motor protein, directly interacts with a PIP3-interacting protein, PIP3BP, and mediates the transport of PIP3-containing vesicles. Recombinant GAKIN and PIP3BP form a complex on synthetic liposomes containing PIP3 and support the motility of the liposomes along microtubules in vitro. In PC12 cells and cultured hippocampal neurons, transport activity of GAKIN contributes to the accumulation of PIP3 at the tip of neurites. In hippocampal neurons, altered accumulation of PIP3 by overexpression of GAKIN constructs led to the loss of the axonally differentiated neurites. Together, these results suggest that, in neurons, the GAKIN-PIP3BP complex transports PIP3 to the neurite ends and regulates neuronal polarity formation. FAU - Horiguchi, Kaori AU - Horiguchi K AD - Department of Pharmacology and Cancer Center, University of Illinois College of Medicine, Chicago, IL 60612, USA. FAU - Hanada, Toshihiko AU - Hanada T FAU - Fukui, Yasuhisa AU - Fukui Y FAU - Chishti, Athar H AU - Chishti AH LA - eng GR - R01 CA094414/CA/NCI NIH HHS/United States GR - CA 94414/CA/NCI NIH HHS/United States GR - HL60755/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20060724 PL - United States TA - J Cell Biol JT - The Journal of cell biology JID - 0375356 RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (Liposomes) RN - 0 (Molecular Motor Proteins) RN - 0 (Phosphatidylinositol Phosphates) RN - 0 (phosphatidylinositol 3,4,5-triphosphate) RN - EC 3.6.1.- (KIF13B protein, human) RN - EC 3.6.4.4 (Kinesins) SB - IM MH - Adaptor Proteins, Signal Transducing/metabolism MH - Animals MH - Biological Transport MH - COS Cells MH - Cattle MH - *Cell Polarity MH - Cells, Cultured MH - Chlorocebus aethiops MH - Humans MH - Kinesins/chemistry/*metabolism MH - Liposomes/metabolism MH - Mice MH - Microtubules/metabolism MH - Models, Biological MH - Molecular Motor Proteins/metabolism MH - Neurons/*cytology MH - PC12 Cells MH - Phosphatidylinositol Phosphates/*metabolism MH - Protein Binding MH - Protein Structure, Tertiary MH - Rats PMC - PMC2064238 EDAT- 2006/07/26 09:00 MHDA- 2006/09/20 09:00 PMCR- 2007/01/31 CRDT- 2006/07/26 09:00 PHST- 2006/07/26 09:00 [pubmed] PHST- 2006/09/20 09:00 [medline] PHST- 2006/07/26 09:00 [entrez] PHST- 2007/01/31 00:00 [pmc-release] AID - jcb.200604031 [pii] AID - 200604031 [pii] AID - 10.1083/jcb.200604031 [doi] PST - ppublish SO - J Cell Biol. 2006 Jul 31;174(3):425-36. doi: 10.1083/jcb.200604031. Epub 2006 Jul 24.