Snx5, as a Mind bomb-binding protein, is expressed in hematopoietic and endothelial precursor cells in zebrafish.
Notch signaling has an evolutionarily conserved function for cell fate determination and stem cell maintenance. Previously, we identified a novel component of the Notch signaling pathway in zebrafish, mind bomb, which encodes an E3 ubiquitin ligase essential for Notch signal activation. Further studies showed that Mind bomb(-/-) mouse embryos exhibited pan-Notch phenotypes in various tissues, suggesting that Mind bomb function is conserved in mammals. Therefore we sought to understand the various molecular partners of Mind bomb using yeast two-hybrid screening. In this search we identified Sorting nexin 5 (Snx5) as a novel interacting partner of Mind bomb. Furthermore we demonstrated that Snx5 colocalizes with Mind bomb in early endosomal compartments, suggesting that Snx5 is important for Mind bomb trafficking. In addition, we identified zebrafish orthologue of Snx5 and showed that snx5 is predominantly expressed in hematopoietic and endothelial precursor cells in zebrafish. We also found defects in hematopoiesis and blood vessel development in snx5 morpholino-injected embryos. Taken together, we show that Snx5, a novel interacting partner of Mind bomb, may have an essential role for cell fate determination in early development.
Yoo
Kyeong-Won
KW
Department of Biology, Chungnam National University, Daejeon 305-764, South Korea.
Kim
Eun-Hye
EH
Jung
Seung-Hyun
SH
Rhee
Myungchull
M
Koo
Bon-Kyoung
BK
Yoon
Ki-Jun
KJ
Kong
Young-Yun
YY
Kim
Cheol-Hee
CH
D000818:Animals; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D051379:Mice; D018919:Neovascularization, Physiologic; D058305:Sorting Nexins; D013234:Stem Cells / Q000378:metabolism; D020798:Two-Hybrid System Techniques; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry / Q000378:metabolism*; D033921:Vesicular Transport Proteins; D015027:Zebrafish / Q000196:embryology* / Q000378:metabolism; D029961:Zebrafish Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*
D002352:Carrier Proteins; C402667:SNX5 protein, human; C513495:Snx5 protein, zebrafish; D058305:Sorting Nexins; D033921:Vesicular Transport Proteins; D029961:Zebrafish Proteins; C513496:MIB1 ligase, human; D044767:Ubiquitin-Protein Ligases