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Lin DC , Quevedo C , Brewer NE , Bell A , Testa JR , Grimes ML , Miller FD , Kaplan DR
APPL1 associates with TrkA and GIPC1 and is required for nerve growth factor-mediated signal transduction
Molecular and Cellular Biology. 2006 Dec;26(23) :8928-8941
PMID: ISI:000242203700022   
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Abstract
The neurotrophin receptor TrkA plays critical roles in the nervous system by recruiting signaling molecules that activate pathways required for the growth and survival of neurons. Here, we report APPL1 as a TrkA-associated protein. APPL1 and TrkA coirnmunoprecipitated in sympathetic neurons. We have identified two routes through which this association can occur. APPL1 was isolated as a binding partner for the TrkA-interacting protein GIPC1 from rat brain lysate by mass spectrometry. The PDZ domain of GIPC1 directly engaged the C-terminal sequence of APPL1. This interaction provides a means through which APPL1 may be recruited to TrkA. In addition, the APPL1 PTB domain bound to TrkA, indicating that APPL1 may associate with TrkA independently of GIPC1. Isolation of endosomal fractions by high-resolution centrifugation determined that APPL1, GIPC1, and phosphorylated TrkA are enriched in the same fractions. Reduction of APPL1 or GIPC1 protein levels suppressed nerve growth factor (NGF)-dependent MEK, extracellular signal-regulated kinase, and AM activation and neurite outgrowth in PC12 cells. Together, these results indicate that GIPC1 and APPL1 play a role in TrkA function and suggest that a population of endosomes bearing a complex of APPL1, GIPC1, and activated TrkA may transmit NGF signals.
Notes
ISI Document Delivery No.: 107XG Times Cited: 1 Cited Reference Count: 41 Cited References: ASCHENBRENNER L, 2003, MOL BIOL CELL, V14, P2728 BEATTIE EC, 1996, COLD SPRING HARB SYM, V61, P389 BELLIVEAU DJ, 1997, J CELL BIOL, V136, P375 BHATTACHARYYA A, 1997, J NEUROSCI, V17, P7007 BUNN RC, 1999, MOL BIOL CELL, V10, P819 DELCROIX JD, 2003, NEURON, V39, P69 EHLERS MD, 1995, J CELL BIOL, V130, P149 ENGQVISTGOLDSTEIN AEY, 1999, J CELL BIOL, V147, P1503 GINTY DD, 2002, CURR OPIN NEUROBIOL, V12, P268 GRIMES ML, 1996, J NEUROSCI, V16, P7950 GRIMES ML, 1997, P NATL ACAD SCI USA, V94, P9909 HEMPSTEAD BL, 1992, NEURON, V9, P883 HENKEMEYER M, 1994, ONCOGENE, V9, P1001 HOWE CL, 2001, NEURON, V32, P801 HOWE CL, 2004, J NEUROBIOL, V58, P207 JEANNETEAU F, 2004, MOL BIOL CELL, V15, P4926 JEANNETEAU F, 2004, MOL BIOL CELL, V15, P696 JOHANSON SO, 1995, BRAIN RES, V690, P55 KAPLAN DR, 2000, CURR OPIN NEUROBIOL, V10, P381 LAVOIE JF, 2005, J BIOL CHEM, V280, P29199 LEVIMONTALCINI R, 1966, HARVEY LECT, V60, P217 LEVIMONTALCINI R, 1987, SCIENCE, V237, P1154 LOU XJ, 2001, MOL BIOL CELL, V12, P615 LOU XJ, 2002, J AM SOC NEPHROL, V13, P918 MAZZONI IE, 1999, J NEUROSCI, V19, P9716 MIACZYNSKA M, 2004, CELL, V116, P445 MITSUUCHI Y, 1999, ONCOGENE, V18, P4891 PATAPOUTIN A, 2001, CURR OPIN NEUROBIOL, V11, P272 RODMAN JS, 2000, J CELL SCI, V113, P183 SAXENA S, 2005, J NEUROSCI, V25, P10930 SHAO YF, 2002, J CELL BIOL, V157, P679 TSUIPIERCHALA BA, 1999, J NEUROSCI, V19, P8207 VAILLANT AR, 2002, NEURON, V34, P985 VALDEZ G, 2005, J NEUROSCI, V25, P5236 WARTIOVAARA K, 2002, J NEUROSCI, V22, P815 WASIAK S, 2002, J CELL BIOL, V158, P855 WATSON FL, 1999, J NEUROSCI, V19, P7889 YANG L, 2003, J BIOL CHEM, V278, P16820 YANO H, 2005, NEUROCHEM RES, V30, P767 YE HH, 2003, NEURON, V39, P57 ZERIAL M, 2001, NAT REV MOL CELL BIO, V2, P107