Frontiers in Molecular Neuroscience (Sep 2016)
Integrin activation through the hematopoietic adapter molecule ADAP regulates dendritic development of hippocampal neurons
Abstract
Integrin-mediated cell adhesion and signaling is of critical importance for neuronal differentiation. Recent evidence suggests that an inside-out activation of β1-integrin, similar to that observed in hematopoietic cells, contributes to the growth and branching of dendrites. In this study we investigated the role of the hematopoietic adaptor protein ADAP in these processes. We demonstrate the expression of ADAP in the developing and adult nervous hippocampus, and in outgrowing dendrites of primary hippocampal neurons. We further show that ADAP occurs in a complex with another adaptor protein SKAP-HOM, with the Rap1 effector protein RAPL and the Hippo kinase MST1, resembling an ADAP/SKAP module that has been previously described in T cells and is critically involved in inside-out activation of integrins. Knock down of ADAP resulted in reduced expression of activated β1-integrin on dendrites. It furthermore reduced the differentiation of developing neurons, as indicated by reduced dendrite growth and decreased expression of the dendritic marker MAP2. Our data suggest that an ADAP-dependent integrin-activation similar to that described in hematopoietic cells contributes to the differentiation of neuronal cells.
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