2010 Fiscal Year Final Research Report
The role of macropinocytosis in repulsive axon guidance
| Project/Area Number |
19700302
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Neuroscience in general
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| Research Institution | The Institute of Physical and Chemical Research |
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Principal Investigator |
KABAYAMA Hiroyuki The Institute of Physical and Chemical Research, 発生神経生物研究チーム, 客員研究員 (10332339)
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| Project Period (FY) |
2007 – 2010
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| Keywords | マクロピノサイトーシス / 成長円錐退縮 / 反発性軸索誘導 / syntaxin1B |
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| Research Abstract |
Growth cone collapse is a crucial process for repulsive axon guidance and is accompanied by a reduction in growth cone surface area. This process of reduction may be regulated by endocytosis; however, its molecular mechanism is unclear. Macropinocytosis is a clathrin-independent form of endocytosis in which large areas of plasma membrane can be engulfed. We have reported previously that macropinocytosis is induced in growth cones of chick dorsal root ganglion neurons by semaphorin 3A (Sema3A), a repulsive axon guidance cue, and that Sema3A-induced reduction in growth cone surface area and macropinocytic vacuole area were correlated, suggesting a positive role for macropinocytosis in Sema3A-induced growth cone collapse. In the present study, we found that syntaxin 1B (Syx1B), a membrane trafficking protein, is a negative regulator of macropinocytosis, and its expression is downregulated by Sema3A signaling. Macropinocytosis inhibitor ethylisopropylamiloride or Syx1B overexpression suppressed Sema3A-induced macropinocytosis and growth cone collapse. These results indicate that Syx1B couples macropinocytosis-mediated massive internalization of the plasma membrane to Sema3A-induced growth cone collapse.
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