The Exocyst Complex Associates with Microtubules to Mediate Vesicle Targeting and Neurite Outgrowth
During neuronal development, vesicles are targeted to the growth cone to promote neurite outgrowth and synaptogenesis. The Exocyst complex is an essential macromolecule in the secretory pathway that may play a role in vesicle targeting. Although it has been shown that this complex is enriched in rat...
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Published in | The Journal of neuroscience Vol. 21; no. 11; pp. 3839 - 3848 |
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Main Authors | , |
Format | Journal Article |
Language | English |
Published |
United States
Soc Neuroscience
01.06.2001
Society for Neuroscience |
Subjects | |
Online Access | Get full text |
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Abstract | During neuronal development, vesicles are targeted to the growth cone to promote neurite outgrowth and synaptogenesis. The Exocyst complex is an essential macromolecule in the secretory pathway that may play a role in vesicle targeting. Although it has been shown that this complex is enriched in rat brain, the molecular mechanism underlying its function is largely unknown. Here, we report that the Exocyst complex coimmunoprecipitates with microtubules from total rat brain lysate. Additionally, the Exocyst complex subcellular localization changes on neuronal differentiation. In undifferentiated pheochromocytoma (PC12) cells, this complex is associated with microtubules at the microtubule organizing center. However, in differentiated PC12 cells and cultured hippocampal neurons, the Exocyst complex and microtubules extend to the growing neurite and colocalize at the growth cone with synaptotagmin. Inhibition of the NGF-activated MAP kinase pathway blocks the Exocyst complex and microtubule redistribution, abolishing neurite outgrowth and promoting cytosolic accumulation of secretory vesicles. Consistently, the overexpression of Exocyst sec10 subunit mutant blocks neurite outgrowth. These results indicate that the Exocyst complex targets secretory vesicles to specific domains of the plasma membrane through its association with the microtubules, promoting neurite outgrowth. |
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AbstractList | During neuronal development, vesicles are targeted to the growth cone to promote neurite outgrowth and synaptogenesis. The Exocyst complex is an essential macromolecule in the secretory pathway that may play a role in vesicle targeting. Although it has been shown that this complex is enriched in rat brain, the molecular mechanism underlying its function is largely unknown. Here, we report that the Exocyst complex coimmunoprecipitates with microtubules from total rat brain lysate. Additionally, the Exocyst complex subcellular localization changes on neuronal differentiation. In undifferentiated pheochromocytoma (PC12) cells, this complex is associated with microtubules at the microtubule organizing center. However, in differentiated PC12 cells and cultured hippocampal neurons, the Exocyst complex and microtubules extend to the growing neurite and colocalize at the growth cone with synaptotagmin. Inhibition of the NGF-activated MAP kinase pathway blocks the Exocyst complex and microtubule redistribution, abolishing neurite outgrowth and promoting cytosolic accumulation of secretory vesicles. Consistently, the overexpression of Exocyst
sec10
subunit mutant blocks neurite outgrowth. These results indicate that the Exocyst complex targets secretory vesicles to specific domains of the plasma membrane through its association with the microtubules, promoting neurite outgrowth. During neuronal development, vesicles are targeted to the growth cone to promote neurite outgrowth and synaptogenesis. The Exocyst complex is an essential macromolecule in the secretory pathway that may play a role in vesicle targeting. Although it has been shown that this complex is enriched in rat brain, the molecular mechanism underlying its function is largely unknown. Here, we report that the Exocyst complex coimmunoprecipitates with microtubules from total rat brain lysate. Additionally, the Exocyst complex subcellular localization changes on neuronal differentiation. In undifferentiated pheochromocytoma (PC12) cells, this complex is associated with microtubules at the microtubule organizing center. However, in differentiated PC12 cells and cultured hippocampal neurons, the Exocyst complex and microtubules extend to the growing neurite and colocalize at the growth cone with synaptotagmin. Inhibition of the NGF-activated MAP kinase pathway blocks the Exocyst complex and microtubule redistribution, abolishing neurite outgrowth and promoting cytosolic accumulation of secretory vesicles. Consistently, the overexpression of Exocyst sec10 subunit mutant blocks neurite outgrowth. These results indicate that the Exocyst complex targets secretory vesicles to specific domains of the plasma membrane through its association with the microtubules, promoting neurite outgrowth. |
Author | Hsu, Shu-Chan Vega, Irving E |
AuthorAffiliation | 2 Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, New Jersey 08854 1 Department of Biochemistry, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, and |
AuthorAffiliation_xml | – name: 1 Department of Biochemistry, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, and – name: 2 Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, New Jersey 08854 |
Author_xml | – sequence: 1 fullname: Vega, Irving E – sequence: 2 fullname: Hsu, Shu-Chan |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/11356872$$D View this record in MEDLINE/PubMed |
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Snippet | During neuronal development, vesicles are targeted to the growth cone to promote neurite outgrowth and synaptogenesis. The Exocyst complex is an essential... |
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SubjectTerms | Animals Brain Chemistry Calcium-Binding Proteins Cell Differentiation - physiology Cells, Cultured Enzyme Inhibitors - pharmacology Exocyst complex Exocytosis - physiology Growth Cones - metabolism Growth Cones - ultrastructure Hippocampus - cytology Hippocampus - metabolism Macromolecular Substances MAP Kinase Signaling System - drug effects Membrane Glycoproteins - metabolism Mice Mice, Inbred BALB C Microtubule-Organizing Center - metabolism Microtubules - chemistry Microtubules - drug effects Microtubules - metabolism Nerve Growth Factor - pharmacology Nerve Tissue Proteins - metabolism Neurites - metabolism Neurites - ultrastructure Neurons - metabolism Neurons - ultrastructure PC12 Cells Precipitin Tests Protein Synthesis Inhibitors - pharmacology Rats Secretory Vesicles - metabolism Synaptotagmins |
Title | The Exocyst Complex Associates with Microtubules to Mediate Vesicle Targeting and Neurite Outgrowth |
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