Sortilin regulates sorting and secretion of Sonic hedgehog.

Autor:	Campbell C; Regenerative Medicine Program, Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, Ontario, Canada K1H 8L6 Department of Cellular and Molecular Medicine, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H 8M5., Beug S; Regenerative Medicine Program, Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, Ontario, Canada K1H 8L6 Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H 8M5., Nickerson PE; Vision Science Division, Krembil Research Institute, University Health Network and Department of Ophthalmology and Vision Sciences, University of Toronto, 60 Leonard Street, Toronto ON M5T 2S8., Peng J; Department of Biology, McGill University, 1205 Ave Docteur Penfield Room W4/8, Montreal, Quebec, Canada H3A 1B1 Institut de recherches cliniques de Montréal (IRCM), 110 Avenue des Pins Ouest, Montréal, Quebec, Canada H2W 1R7., Mazerolle C; Regenerative Medicine Program, Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, Ontario, Canada K1H 8L6., Bassett EA; Regenerative Medicine Program, Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, Ontario, Canada K1H 8L6., Ringuette R; Regenerative Medicine Program, Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, Ontario, Canada K1H 8L6 Department of Cellular and Molecular Medicine, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H 8M5., Jama FA; Regenerative Medicine Program, Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, Ontario, Canada K1H 8L6 Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H 8M5., Morales C; Department of Anatomy and Cell Biology, McGill University, 3640 Rue University, Montréal, Quebec, Canada H3A 0C7., Christ A; Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Str. 10, 13125 Berlin, Germany., Wallace VA; Regenerative Medicine Program, Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, Ontario, Canada K1H 8L6 Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H 8M5 Vision Science Division, Krembil Research Institute, University Health Network and Department of Ophthalmology and Vision Sciences, University of Toronto, 60 Leonard Street, Toronto ON M5T 2S8 vwallace@uhnresearch.ca.
Jazyk:	angličtina
Zdroj:	Journal of cell science [J Cell Sci] 2016 Oct 15; Vol. 129 (20), pp. 3832-3844. Date of Electronic Publication: 2016 Sep 15.
DOI:	10.1242/jcs.183541
Abstrakt:	Sonic Hedgehog (Shh) is a secreted morphogen that is an essential regulator of patterning and growth. The Shh full-length protein undergoes autocleavage in the endoplasmic reticulum to generate the biologically active N-terminal fragment (ShhN), which is destined for secretion. We identified sortilin (Sort1), a member of the VPS10P-domain receptor family, as a new Shh trafficking receptor. We demonstrate that Sort-Shh interact by performing coimmunoprecipitation and proximity ligation assays in transfected cells and that they colocalize at the Golgi. Sort1 overexpression causes re-distribution of ShhN and, to a lesser extent, of full-length Shh to the Golgi and reduces Shh secretion. We show loss of Sort1 can partially rescue Hedgehog-associated patterning defects in a mouse model that is deficient in Shh processing, and we show that Sort1 levels negatively regulate anterograde Shh transport in axons in vitro and Hedgehog-dependent axon-glial interactions in vivo Taken together, we conclude that Shh and Sort1 can interact at the level of the Golgi and that Sort1 directs Shh away from the pathways that promote its secretion. (© 2016. Published by The Company of Biologists Ltd.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu