Kermit 2/XGIPC, an IGF1 receptor interacting protein, is required for IGF signaling in Xenopus eye development.
GIPC is a PDZ-domain-containing protein identified in vertebrate and invertebrate organisms through its interaction with a variety of binding partners including many membrane proteins. Despite the multiple reports identifying GIPC, its endogenous function and the physiological significance of these interactions are much less studied. We have previously identified the Xenopus GIPC homolog kermit as a frizzled 3 interacting protein that is required for frizzled 3 induction of neural crest in ectodermal explants. We identified a second Xenopus GIPC homolog, named kermit 2 (also recently described as an IGF receptor interacting protein and named XGIPC). Despite its high amino acid similarity with kermit, kermit 2/XGIPC has a distinct function in Xenopus embryos. Loss-of-function analysis indicates that kermit 2/XGIPC is specifically required for Xenopus eye development. Kermit 2/XGIPC functions downstream of IGF in eye formation and is required for maintaining IGF-induced AKT activation. A constitutively active PI3 kinase partially rescues the Kermit 2/XGIPC loss-of-function phenotype. Our results provide the first in vivo loss of function analysis of GIPC in embryonic development and also indicate that kermit 2/XGIPC is a novel component of the IGF pathway, potentially functioning through modulation of the IGF1 receptor.
Wu
Jinling
J
Cell and Molecular Biology Graduate Group, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
O'Donnell
Michael
M
Gitler
Aaron D
AD
Klein
Peter S
PS
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D000818:Animals; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D005123:Eye / Q000196:embryology / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D015151:Immunoblotting; D047468:Immunoprecipitation; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D010641:Phenotype; D011485:Protein Binding; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D014981:Xenopus / Q000196:embryology / Q000235:genetics*; D029867:Xenopus Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; C438192:GIPC1 protein, Xenopus; D009419:Nerve Tissue Proteins; D029867:Xenopus Proteins; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D051057:Proto-Oncogene Proteins c-akt