PMID- 24407591 OWN - NLM STAT- MEDLINE DCOM- 20140424 LR - 20211203 IS - 1522-1547 (Electronic) IS - 0193-1857 (Print) IS - 0193-1857 (Linking) VI - 306 IP - 5 DP - 2014 Mar 1 TI - Rab1a regulates sorting of early endocytic vesicles. PG - G412-24 LID - 10.1152/ajpgi.00118.2013 [doi] AB - We previously reported that Rab1a is associated with asialoorosomucoid (ASOR)-containing early endocytic vesicles, where it is required for their microtubule-based motility. In Rab1a knockdown (KD) cell lines, ASOR failed to segregate from its receptor and, consequently, did not reach lysosomes for degradation, indicating a defect in early endosome sorting. Although Rab1 is required for Golgi/endoplasmic reticulum trafficking, this process was unaffected, likely due to retained expression of Rab1b in these cells. The present study shows that Rab1a has a more general role in endocytic vesicle processing that extends to EGF and transferrin (Tfn) trafficking. Compared with results in control Huh7 cells, EGF accumulated in aggregates within Rab1a KD cells, failing to reach lysosomal compartments. Tfn, a prototypical example of recycling cargo, accumulated in a Rab11-mediated slow-recycling compartment in Rab1a KD cells, in contrast to control cells, which sort Tfn into a fast-recycling Rab4 compartment. These data indicate that Rab1a is an important regulator of early endosome sorting for multiple cargo species. The effectors and accessory proteins recruited by Rab1a to early endocytic vesicles include the minus-end-directed kinesin motor KifC1, while others remain to be discovered. FAU - Mukhopadhyay, Aparna AU - Mukhopadhyay A AD - Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, New York; FAU - Quiroz, Jose A AU - Quiroz JA FAU - Wolkoff, Allan W AU - Wolkoff AW LA - eng GR - DK-098408/DK/NIDDK NIH HHS/United States GR - P30 DK041296/DK/NIDDK NIH HHS/United States GR - T34 GM008718/GM/NIGMS NIH HHS/United States GR - DK-23026/DK/NIDDK NIH HHS/United States GR - DK-41908/DK/NIDDK NIH HHS/United States GR - DK-41296/DK/NIDDK NIH HHS/United States GR - R01 DK098408/DK/NIDDK NIH HHS/United States GR - T32 GM007288/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20140109 PL - United States TA - Am J Physiol Gastrointest Liver Physiol JT - American journal of physiology. Gastrointestinal and liver physiology JID - 100901227 RN - 0 (Asialoglycoproteins) RN - 0 (KIFC1 protein, human) RN - 0 (asialoovomucoid) RN - 37281-36-0 (Ovomucin) RN - EC 3.6.4.4 (Kinesins) RN - EC 3.6.5.2 (rab1 GTP-Binding Proteins) SB - IM MH - Asialoglycoproteins/metabolism MH - Biological Transport MH - Cell Line, Tumor MH - Endocytosis MH - Fluorescent Antibody Technique MH - Gene Expression Regulation/*physiology MH - Gene Knockdown Techniques MH - Humans MH - Kinesins/genetics/metabolism MH - Ovomucin/metabolism MH - Transport Vesicles/*physiology MH - rab1 GTP-Binding Proteins/genetics/*metabolism PMC - PMC3949023 OTO - NOTNLM OT - EGF OT - Rab1a OT - endocytosis OT - sorting OT - transferrin EDAT- 2014/01/11 06:00 MHDA- 2014/04/25 06:00 PMCR- 2015/03/01 CRDT- 2014/01/11 06:00 PHST- 2014/01/11 06:00 [entrez] PHST- 2014/01/11 06:00 [pubmed] PHST- 2014/04/25 06:00 [medline] PHST- 2015/03/01 00:00 [pmc-release] AID - ajpgi.00118.2013 [pii] AID - GI-00118-2013 [pii] AID - 10.1152/ajpgi.00118.2013 [doi] PST - ppublish SO - Am J Physiol Gastrointest Liver Physiol. 2014 Mar 1;306(5):G412-24. doi: 10.1152/ajpgi.00118.2013. Epub 2014 Jan 9.