Teodorof C, Divakar S, Soontornniyomkij B, Achim C L, Kaul M, Singh K K
Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA.
Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA.
Neurobiol Dis. 2014 Sep;69:54-64. doi: 10.1016/j.nbd.2014.05.002. Epub 2014 May 11.
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.
人类免疫缺陷病毒1型（HIV-1）在感染早期进入大脑，导致严重的神经元损伤和中枢神经系统损害。HIV-1包膜糖蛋白120（gp120）作为一种神经毒素，在神经元内进行细胞内运输；然而，gp120在神经元中的运输机制尚不清楚。我们的结果表明，与gp120上的N-连接甘露糖残基结合的甘露糖结合凝集素（MBL），参与gp120在神经元亚细胞器中的囊泡内包装，以及这些囊泡在神经元细胞中的亚细胞运输。观察到核周MBL:gp120囊泡复合物，并且MBL通过内质网（ER）和高尔基体囊泡促进gp120的亚细胞运输。MBL的功能性碳水化合物识别结构域是MBL:gp120囊泡复合物核周组织、分布和亚细胞运输所必需的。诺考达唑是一种使微管网络解聚的药物，它消除了MBL:gp120囊泡的运输，这表明这些囊泡复合物是沿着微管网络运输的。活细胞成像证实了MBL:gp120复合物与在神经元胞体和神经突中进行运输的动态亚细胞囊泡的关联。因此，我们的研究结果表明，细胞内MBL在神经元中以微管依赖机制介导病毒糖蛋白的亚细胞运输。
