Polarized signaling endosomes coordinate BDNF-induced chemotaxis of cerebellar precursors (Neuron, 2007, 55:53-68)

報告日期: 2009/05/01
報告時間: 16:00/16:50
報告學生: 謝崇斌
講評老師: 許桂森
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/980501-2.pdf

Polarized Signaling Endosomes Coordinate BDNF Induced Chemotaxis of Cerebellar Precursors

 

Neuron; 2007

 

Speaker: Chung-Pin Hsieh (謝崇斌)

Commentator: Dr. Kuei-Sen Hsu (許桂森)

 

Abstract

Cell polarization induced by chemotaxin provides the direction of cell migration; however, the related mechanism remains unclear. Radial migration of cerebellar granular cell precursors (GCPs) from external granular layer (EGL) into internal granular layer (IGL) provides a good model to discover. BDNF-/- mice showed the impairment of GCPs radial migration, and higher level of BDNF in IGL than in EGL showed a concentration gradient during radial migration (1). This study tried to clarify whether BDNF was involved in the chemotaxin inducing GCPs polarization and discovered the related mechanism. BDNF gradient treatment promotes directional migration of GCPs and accumulation of TrkB receptor in the leading process. BDNF-induced endocytosis of TrkB receptor in the polarization side was essential for directional migration and was not found in the absence of endogenous BDNF.  Activation of TrkB receptor stimulated BDNF release provided amplification of gradient. Downstream effectors of BDNF, PI3 kinase and Tiam1-regulated Rac were involved in the BDNF-induced directional movement, and both effectors colocalized with internalized TrkB receptor induced by BDNF gradient. Taken together, regulated release of BDNF and TrkB endocytosis provide the direction of GCPs polarization and migration along the BDNF gradient.

 

1.     Borghesani, P.R., Peyrin, J.M., Klein, R., Rubin, J., Carter, A.R., Schwartz, P.M., Luster, A., Corfas, G., and Segal, R.A. (2002). BDNF stimulates migration of cerebellar granule cells. Development 129, 1435–1442.