title: RAB-6.1 and RAB-6.2 Promote Retrograde Transport in C. elegans.
abstract: Retrograde transport is a critical mechanism for recycling certain membrane cargo. Following endocytosis from the plasma membrane, retrograde cargo is moved from early endosomes to Golgi followed by transport (recycling) back to the plasma membrane. The complete molecular and cellular mechanisms of retrograde transport remain unclear. The small GTPase RAB-6.2 mediates the retrograde recycling of the AMPA-type glutamate receptor (AMPAR) subunit GLR-1 in C. elegans neurons. Here we show that RAB-6.2 and a close paralog, RAB-6.1, together regulate retrograde transport in both neurons and non-neuronal tissue. Mutants for rab-6.1 or rab-6.2 fail to recycle GLR-1 receptors, resulting in GLR-1 turnover and behavioral defects indicative of diminished GLR-1 function. Loss of both rab-6.1 and rab-6.2 results in an additive effect on GLR-1 retrograde recycling, indicating that these two C. elegans Rab6 isoforms have overlapping functions. MIG-14 (Wntless) protein, which undergoes retrograde recycling, undergoes a similar degradation in intestinal epithelia in both rab-6.1 and rab-6.2 mutants, suggesting a broader role for these proteins in retrograde transport. Surprisingly, MIG-14 is localized to separate, spatially segregated endosomal compartments in rab-6.1 mutants compared to rab-6.2 mutants. Our results indicate that RAB-6.1 and RAB-6.2 have partially redundant functions in overall retrograde transport, but also have their own unique cellular- and subcellular functions.
authors.affiliation: The Waksman Institute, Department of Genetics, Rutgers The State University of New Jersey, Piscataway, New Jersey, United States of America.
authors.forename: Donglei
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Biological Sciences, Tata Institute of Fundamental Research, Colaba, Mumbai, India.|Institute for Stem Cell Biology and Regenerative Medicine (InStem), Bangalore, India.|Manipal University, Karnataka, India.
authors.forename: Jyoti
authors.initials: J
authors.lastname: Dubey
authors.affiliation: Department of Biological Sciences, Tata Institute of Fundamental Research, Colaba, Mumbai, India.
authors.forename: Sandhya P
authors.initials: SP
authors.lastname: Koushika
authors.affiliation: The Waksman Institute, Department of Genetics, Rutgers The State University of New Jersey, Piscataway, New Jersey, United States of America.
authors.forename: Christopher
authors.initials: C
authors.lastname: Rongo
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism; D015870:Gene Expression; D006056:Golgi Apparatus / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism; D021381:Protein Transport; D018091:Receptors, AMPA / Q000378:metabolism; D016415:Sequence Alignment; D020691:rab GTP-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; C527888:Mig-14 protein, C elegans; D018091:Receptors, AMPA; C096470:glr-1 protein, C elegans; C571036:RAB-6.2 protein, C elegans; D020691:rab GTP-Binding Proteins