BWincklerheader

BWinckler

Associate Professor of Neuroscience
Ph.D. 1994, Massachusetts Institute of Technology

bwinckler@virginia.edu
(434)924-5528 office
(434)924-5526 lab

Membrane traffic and membrane domains in polarized neurons

I am a cellular neurobiologist interested in the morphogenesis of vertebrate neurons. Neurons are highly polarized cells which extend two distinct kinds of processes, axons and dendrites.  Axons and dendrites carry out different functions.  Dendrites receive synaptic inputs.  Axons, on the other hand, propagate action potentials along their lengths and, at the nerve terminal, convert this electrical signal into a chemical one. Axons and dendrites differ from each other in the composition and arrangement of cytoskeletal elements, in the distribution of organelles, the composition of proteins in the plasma membrane, among others.  Having these two distinct membrane domains is critical to ensure the vectorial propagation of nerve impulses.  The question I am studying is how these two distinct domains are set up.  How are membrane proteins sorted on their biosynthetic route to either axons or dendrites?  What is the machinery?  What are the signals?  How are membrane proteins maintained in the correct domain once they reach it?  The approaches used include transfection of primary neurons via adenoviral vectors, live-cell imaging, measurements of lateral mobility of membrane proteins using optical tweezers and cell fractionation.

Winckler image

Selected publications:

Yap, C.C., D. Wisco, P. Kujala, Z.M. Lasiecka, J.T. Cannon, M.C. Chang, H. Hirling, J. Klumperman, B. Winckler.  "The somatodendritic endosomal regulator NEEP21 facilitates axonal targeting of NgCAM." Journal of Cell Biology 180:827-842 (2008).

Boiko, T., M. Vakulenko, H. Ewers, C. Norden, C.C. Yap, B. Winckler. "Ankyrin-dependent and -independent mechanisms orchestrate axonal compartmentalization of L1 family members neurofascin and L1/NgCAM". J. Neuroscience 27:590-603 (2007).

Boiko, T. and B. Winckler.  "Myelin under construction - teamwork required."  J. Cell Biology 172:799-801 (2006).

Johnson, E.M., Y. Kinoshita, D. B. Weinreb, M. J. Wortman, R. Simon, K. Kalili, B. Winckler,and J. Gordon.  "Role of Pur? in targeting mRNA to sites of translation in hippocampal neuronal dendrites.:  J. Neurosci Res.  83:  929 (2006).

Chang, MC,  Wisco, D,  Ewers, H, Norden, C, and Winckler, B. "Inhibition of sphingolipid synthesis affects kinetics but not fidelity of L1/NgCAM transport along direct but not transcytotic pathways." Mol. Cell Neuroscience 13:525-538(2006).

Anderson, ED, Maday, S, Sfakianos, J, Hull, M, Winckler, B, Sheff, D,  Fölsch, H,  and Mellman, I. "Transcytosis of L1/NgCAM in epithelial cells reflects differential adaptor recognition on the endocytic and secretory pathways." J. Cell Biology 170:595 (2005).

Winckler, B. "Pathways for axonal targeting of membrane proteins." Biology of the Cell 96:669 (2004).

Wisco, D, Anderson, ED, Chang, MC,  Norden, C, Fölsch, H, Boiko, T, and Winckler, B.  "Uncovering multiple axonal targeting pathways in hippocampal neurons". J. Cell Biology 162:1317-28 (2003).

Boiko, T, and Winckler, B. "Picket and other Fences in Biological Membranes." Dev. Cell 5:191 (2003).

Winckler, B, and Mellman, I. "Neuronal polarity: controlling the sorting and diffusion of membrane components". Neuron 23:637-640 (1999).

Winckler, B, Forscher, P, and Mellman, I.  "Maintaining differential membrane protein distribution in polarized neurons: a diffusion barrier at the axonal initial segment." Nature 397:698-701 (1999).  Highlight in "News and Views": "Sorting out the neuron" Nature 397:653-655 (1999).

Winckler, B, and Poo, M-M. "No diffusion barrier at axon hillock."  Nature 379:213 (1996).