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 gp1...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2014-09-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996114001120 |
| _version_ | 1818675901673504768 |
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| author | C. Teodorof S. Divakar B. Soontornniyomkij C.L. Achim M. Kaul K.K. Singh |
| author_facet | C. Teodorof S. Divakar B. Soontornniyomkij C.L. Achim M. Kaul K.K. Singh |
| author_sort | C. Teodorof |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-17T08:34:57Z |
| format | Article |
| id | doaj.art-31b4513aac45404893a5cd90b608de41 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-17T08:34:57Z |
| publishDate | 2014-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-31b4513aac45404893a5cd90b608de412022-12-21T21:56:30ZengElsevierNeurobiology of Disease1095-953X2014-09-01695464Intracellular mannose binding lectin mediates subcellular trafficking of HIV-1 gp120 in neuronsC. Teodorof0S. Divakar1B. Soontornniyomkij2C.L. Achim3M. Kaul4K.K. Singh5Department of Pediatrics, University of California, San Diego, La Jolla, CA, USADepartment of Pediatrics, University of California, San Diego, La Jolla, CA, USADepartment of Psychiatry, University of California, San Diego, La Jolla, CA, USADepartment of Psychiatry, University of California, San Diego, La Jolla, CA, USADepartment of Psychiatry, University of California, San Diego, La Jolla, CA, USA; Sanford-Burnham Medical Research Institute, 10901 N Torrey Pines Rd, La Jolla, CA, USADepartment of Pediatrics, University of California, San Diego, La Jolla, CA, USA; Corresponding author at: Department of Pediatrics, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0672, USA. Fax: +1 858 534 7411.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.http://www.sciencedirect.com/science/article/pii/S0969996114001120Mannose binding lectinSubcellular traffickingHIV-1 gp120Microtubule associated protein-2Neuronal transport |
| spellingShingle | C. Teodorof S. Divakar B. Soontornniyomkij C.L. Achim M. Kaul K.K. Singh Intracellular mannose binding lectin mediates subcellular trafficking of HIV-1 gp120 in neurons Neurobiology of Disease Mannose binding lectin Subcellular trafficking HIV-1 gp120 Microtubule associated protein-2 Neuronal transport |
| title | Intracellular mannose binding lectin mediates subcellular trafficking of HIV-1 gp120 in neurons |
| title_full | Intracellular mannose binding lectin mediates subcellular trafficking of HIV-1 gp120 in neurons |
| title_fullStr | Intracellular mannose binding lectin mediates subcellular trafficking of HIV-1 gp120 in neurons |
| title_full_unstemmed | Intracellular mannose binding lectin mediates subcellular trafficking of HIV-1 gp120 in neurons |
| title_short | Intracellular mannose binding lectin mediates subcellular trafficking of HIV-1 gp120 in neurons |
| title_sort | intracellular mannose binding lectin mediates subcellular trafficking of hiv 1 gp120 in neurons |
| topic | Mannose binding lectin Subcellular trafficking HIV-1 gp120 Microtubule associated protein-2 Neuronal transport |
| url | http://www.sciencedirect.com/science/article/pii/S0969996114001120 |
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