Integrin activation through the hematopoietic adapter molecule ADAP regulates dendritic development of hippocampal neurons

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 investi...

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Main Authors: Marlen Thiere, Stefanie Kliche, Bettina Müller, Jan Teuber, Isabell Nold, Oliver Stork
Format: Article
Language:English
Published: Frontiers Media S.A. 2016-09-01
Series:Frontiers in Molecular Neuroscience
Subjects:
Online Access:http://journal.frontiersin.org/Journal/10.3389/fnmol.2016.00091/full
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author Marlen Thiere
Stefanie Kliche
Bettina Müller
Jan Teuber
Isabell Nold
Oliver Stork
Oliver Stork
author_facet Marlen Thiere
Stefanie Kliche
Bettina Müller
Jan Teuber
Isabell Nold
Oliver Stork
Oliver Stork
author_sort Marlen Thiere
collection DOAJ
description 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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spelling doaj.art-ede4854d83bd4ddf8bd692f951c3536c2022-12-22T02:10:28ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992016-09-01910.3389/fnmol.2016.00091202869Integrin activation through the hematopoietic adapter molecule ADAP regulates dendritic development of hippocampal neuronsMarlen Thiere0Stefanie Kliche1Bettina Müller2Jan Teuber3Isabell Nold4Oliver Stork5Oliver Stork6Otto von Guericke University MagdeburgOtto von Guericke University MagdeburgOtto von Guericke University MagdeburgOtto von Guericke University MagdeburgOtto von Guericke University MagdeburgOtto von Guericke University MagdeburgCenter for Behavioral Brain SciencesIntegrin-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.http://journal.frontiersin.org/Journal/10.3389/fnmol.2016.00091/fullAdaptor Proteins, Signal TransducingHippocampusPrimary Cell CultureMouseintegrinNeurite outgrowth
spellingShingle Marlen Thiere
Stefanie Kliche
Bettina Müller
Jan Teuber
Isabell Nold
Oliver Stork
Oliver Stork
Integrin activation through the hematopoietic adapter molecule ADAP regulates dendritic development of hippocampal neurons
Frontiers in Molecular Neuroscience
Adaptor Proteins, Signal Transducing
Hippocampus
Primary Cell Culture
Mouse
integrin
Neurite outgrowth
title Integrin activation through the hematopoietic adapter molecule ADAP regulates dendritic development of hippocampal neurons
title_full Integrin activation through the hematopoietic adapter molecule ADAP regulates dendritic development of hippocampal neurons
title_fullStr Integrin activation through the hematopoietic adapter molecule ADAP regulates dendritic development of hippocampal neurons
title_full_unstemmed Integrin activation through the hematopoietic adapter molecule ADAP regulates dendritic development of hippocampal neurons
title_short Integrin activation through the hematopoietic adapter molecule ADAP regulates dendritic development of hippocampal neurons
title_sort integrin activation through the hematopoietic adapter molecule adap regulates dendritic development of hippocampal neurons
topic Adaptor Proteins, Signal Transducing
Hippocampus
Primary Cell Culture
Mouse
integrin
Neurite outgrowth
url http://journal.frontiersin.org/Journal/10.3389/fnmol.2016.00091/full
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