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Neuronal receptors mediating responses to antibody-activated laminin-1

  • Author(s): Ivins, JK
  • Colognato, H
  • Kreidberg, JA
  • Yurchenco, PD
  • Lander, AD
  • et al.
Creative Commons Attribution 4.0 International Public License
Abstract

Embryonic retinal neurons lose the ability to extend neurites on laminin-1 (LN-1) with increasing developmental age yet still do so on other laminin isoforms. However, after treatment of LN-1 with antibodies to 'short- arm' regions or removal of the short arms proteolytically, LN-1 supports attachment and extension of neurites even by late embryonic retinal neurons. We have mapped a domain for antibody-mediated 'activation' of LN-1 to the N- terminal end of the α1 chain. Furthermore, we show that the primary receptors used in the retinal neuron response to 'activated' LN-1 are integrins α3β1 and α6β1; these are the same receptors used by these neurons for outgrowth on other LN isoforms. Interestingly, α3β1 is preferentially involved in neurite outgrowth, whereas α6β1 preferentially mediates attachment and spreading. However, in cultures from α3 integrin- deficient mice, α6β1 mediates retinal ganglion cell neurite out- growth and compensates for the absence of α3β1. Finally, we show that key features of the retinal neuron response to LN-1 also characterize neurons of the hippocampus, thalamus, and cerebral codex; these include poor response to untreated LN-1, extensive neurite outgrowth on antibody-activated LN-1 or on fragment E8, and dependence of this response on integrin α6β1 and at least one other long arm-binding β1 integrin. These data suggest that regulation of LN-1 function via the process of activation could have important consequences for axonal regeneration. Curiously, the data also imply that the mechanism of laminin activation involves enhanced function at sites that cannot be considered cryptic.

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