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  • Title: Intracellular transport and maturation of nascent low density lipoprotein receptor is blocked by mutation in the Ras-related GTP-binding protein, RAB1B.
    Author: Castellano F, Wilson AL, Maltese WA.
    Journal: J Recept Signal Transduct Res; 1995; 15(7-8):847-62. PubMed ID: 8673720.
    Abstract:
    The relationship between the Ras-related GTP-binding protein, Rab1B, and intracellular transport of nascent low density lipoprotein (LDL) receptor was studied in cultured human embryonic kidney cells (line 293) cotransfected with plasmids encoding the LDL-receptor and either wild-type Rab1B or a Rab1B mutant (N121I) known to act as a dominant suppressor of endogenous Rab1B function. [35S]Methionine pulse-chase analysis of immunoprecipitated LDL-receptor indicated that coexpression with Rab1BN121I, but not Rab1BWT, impaired its conversion from the Endo-H-sensitive 120-125 kDa form to the O-glycosylated 160-170 kDa form, consistent with a block in ER-->Golgi trafficking of the nascent receptor. In cells expressing Rab1BN121I, the newly synthesized LDL-receptor was unable to reach the cell surface as evidenced by its inaccessibility to sulfo-NHS-biotin added to the cultures. These observations provide a direct demonstration of Rab protein involvement in LDL receptor trafficking and lend support to the concept of Rab1B as a universal mediator of ER-->Golgi transport of membrane glycoproteins in mammalian cells.
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