Intracellular mannose binding lectin mediates subcellular trafficking of HIV-1 gp120 in neurons.
Human immunodeficiency virus-1 (HIV-1) enters the brain early during infection and leads to severe neuronal damage and central nervous system impairment. HIV-1 envelope glycoprotein 120 (gp120), a neurotoxin, undergoes intracellular trafficking and transport across neurons; however mechanisms of gp120 trafficking in neurons are unclear. Our results show that mannose binding lectin (MBL) that binds to the N-linked mannose residues on gp120, participates in intravesicular packaging of gp120 in neuronal subcellular organelles and also in subcellular trafficking of these vesicles in neuronal cells. Perinuclear MBL:gp120 vesicular complexes were observed and MBL facilitated the subcellular trafficking of gp120 via the endoplasmic reticulum (ER) and Golgi vesicles. The functional carbohydrate recognition domain of MBL was required for perinuclear organization, distribution and subcellular trafficking of MBL:gp120 vesicular complexes. Nocodazole, an agent that depolymerizes the microtubule network, abolished the trafficking of MBL:gp120 vesicles, suggesting that these vesicular complexes were transported along the microtubule network. Live cell imaging confirmed the association of the MBL:gp120 complexes with dynamic subcellular vesicles that underwent trafficking in neuronal soma and along the neurites. Thus, our findings suggest that intracellular MBL mediates subcellular trafficking and transport of viral glycoproteins in a microtubule-dependent mechanism in the neurons.
Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA.
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Teodorof
Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA.
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Divakar
Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA.
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Soontornniyomkij
Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA.
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Achim
Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA; Sanford-Burnham Medical Research Institute, 10901 N Torrey Pines Rd, La Jolla, CA, USA.
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Kaul
Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA. Electronic address: kusingh@ucsd.edu.
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Singh
D015153:Blotting, Western; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D006056:Golgi Apparatus / Q000187:drug effects / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1; D006801:Humans; D047468:Immunoprecipitation; D037601:Mannose-Binding Lectin / Q000235:genetics / Q000378:metabolism*; D018613:Microscopy, Confocal; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D016501:Neurites / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D015739:Nocodazole / Q000494:pharmacology; D015388:Organelles / Q000187:drug effects / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D022161:Transport Vesicles / Q000187:drug effects / Q000378:metabolism; D050257:Tubulin Modulators / Q000494:pharmacology
D015699:HIV Envelope Protein gp120; C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin; D050257:Tubulin Modulators; D015739:Nocodazole
HIV-1 gp120; Mannose binding lectin; Microtubule associated protein-2; Neuronal transport; Subcellular trafficking