title: The role of UDP-Glc:glycoprotein glucosyltransferase 1 in the maturation of an obligate substrate prosaposin.
abstract: An endoplasmic reticulum (ER) quality control system assists in efficient folding and disposal of misfolded proteins. N-linked glycans are critical in these events because their composition dictates interactions with molecular chaperones. UDP-glucose:glycoprotein glucosyltransferase 1 (UGT1) is a key quality control factor of the ER. It adds glucoses to N-linked glycans of nonglucosylated substrates that fail a quality control test, supporting additional rounds of chaperone binding and ER retention. How UGT1 functions in its native environment is poorly understood. The role of UGT1 in the maturation of glycoproteins at basal expression levels was analyzed. Prosaposin was identified as a prominent endogenous UGT1 substrate. A dramatic decrease in the secretion of prosaposin was observed in ugt1(-/-) cells with prosaposin localized to large juxtanuclear aggresome-like inclusions, which is indicative of its misfolding and the essential role that UGT1 plays in its proper maturation. A model is proposed that explains how UGT1 may aid in the folding of sequential domain-containing proteins such as prosaposin.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Massachusetts, Amherst, MA 01003, USA.
authors.forename: Bradley R
authors.initials: BR
authors.lastname: Pearse
authors.forename: Taku
authors.initials: T
authors.lastname: Tamura
authors.forename: Johan C
authors.initials: JC
authors.lastname: Sunryd
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Grabowski
authors.forename: Randal J
authors.initials: RJ
authors.lastname: Kaufman
authors.forename: Daniel N
authors.initials: DN
authors.lastname: Hebert
mesh_terms: D000818:Animals; D016466:CHO Cells; D037281:Calnexin / Q000378:metabolism; D037282:Calreticulin / Q000378:metabolism; D020134:Catalytic Domain / Q000235:genetics; D006224:Cricetinae; D003412:Cricetulus; D003902:Detergents / Q000737:chemistry; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D005964:Glucosyltransferases / Q000235:genetics / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism; D051379:Mice; D009154:Mutation / Q000502:physiology; D011487:Protein Conformation; D017510:Protein Folding; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D049231:Saposins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012995:Solubility; D014746:Vimentin / Q000378:metabolism
chemical_list: D037282:Calreticulin; D003902:Detergents; C483344:Psap protein, mouse; D049231:Saposins; D014746:Vimentin; D037281:Calnexin; D005964:Glucosyltransferases; C072423:mannosylglycoprotein 1,3-glucosyltransferase