0000000000381048
AUTHOR
Elmar Porten
Dystroglycan regulates structure, proliferation and differentiation of neuroepithelial cells in the developing vertebrate CNS.
AbstractIn the developing CNS α- and β-dystroglycan are highly concentrated in the endfeet of radial neuroepithelial cells at the contact site to the basal lamina. We show that injection of anti-dystroglycan Fab fragments, knockdown of dystroglycan using RNAi, and overexpression of a dominant-negative dystroglycan protein by microelectroporation in neuroepithelial cells of the chick retina and optic tectum in vivo leads to the loss of their radial morphology, to hyperproliferation, to an increased number of postmitotic neurons, and to an altered distribution of several basally concentrated proteins. Moreover, these treatments also altered the oriented growth of axons from retinal ganglion c…
The Process-inducing Activity of Transmembrane Agrin Requires Follistatin-like Domains
Clustering or overexpression of the transmembrane form of the extracellular matrix proteoglycan agrin in neurons results in the formation of numerous highly motile filopodia-like processes extending from axons and dendrites. Here we show that similar processes can be induced by overexpression of transmembrane-agrin in several non-neuronal cell lines. Mapping of the process-inducing activity in neurons and non-neuronal cells demonstrates that the cytoplasmic part of transmembrane agrin is dispensable and that the extracellular region is necessary for process formation. Site-directed mutagenesis reveals an essential role for the loop between beta-sheets 3 and 4 within the Kazal subdomain of t…
Clustering transmembrane-agrin induces filopodia-like processes on axons and dendrites
The transmembrane form of agrin (TM-agrin) is primarily expressed in the CNS, particularly on neurites. To analyze its function, we clustered TM-agrin on neurons using anti-agrin antibodies. On axons from the chick CNS and PNS as well as on axons and dendrites from mouse hippocampal neurons anti-agrin antibodies induced the dose- and time-dependent formation of numerous filopodia-like processes. The processes appeared within minutes after antibody addition and contained a complex cytoskeleton. Formation of processes required calcium, could be inhibited by cytochalasine D, but was not influenced by staurosporine, heparin or pervanadate. Time-lapse video microscopy revealed that the processes…