Mouse Rab11-FIP4 regulates proliferation and differentiation of retinal progenitors in a Rab11-independent manner.
We identified Rab11-family interacting protein 4 (Rab11-FIP4) as a gene strongly expressed in the developing mouse retina. The major transcript encoding a full-length protein, mRab11-FIP4A, was expressed predominantly in neural tissues; whereas an alternative transcript encoding an N-terminally truncated form of the protein, mRab11-FIP4B, was expressed ubiquitously as a minor form. Gain-of-function of mRab11-FIP4A in retina promoted cell cycle exit and increased subpopulations of retinal cells localized in the inner nuclear layer, such as bipolar cells and Müller glia. Reversal of the phenotype was observed in the loss-of-function experiment. Furthermore, Shh signaling was suggested to be involved in these functions. Analysis using truncation mutants revealed the essential role of the N-terminal region containing a conserved EF-hand motif for the retinal phenotypes induced by the expression of mRab11-FIP4A, whereas binding to Rab11 was dispensable, suggesting the involvement of a novel Rab11-independent mechanism for mRab11-FIP4A action in the regulation of retinal development.
Muto
Akihiko
A
Department of Molecular and Developmental Biology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, Japan.
Aoki
Yutaka
Y
Watanabe
Sumiko
S
D000818:Animals; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D012160:Retina / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D014162:Transfection; D020691:rab GTP-Binding Proteins / Q000378:metabolism; D000099193:rab11 GTP-Binding Proteins
D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D018076:DNA, Complementary; D053823:Hedgehog Proteins; D009419:Nerve Tissue Proteins; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; C519488:Rab11-FIP4 protein, mouse; C465570:Shh protein, mouse