ARAP1 Bridges Actin Dynamics and AP-3-Dependent Membrane Traffic in Bone-Digesting Osteoclasts
Summary: Bone-resorbing osteoclasts play a central role in bone remodeling and its pathology. To digest bone, osteoclasts re-organize both F-actin, to assemble podosomes/sealing zones, and membrane traffic, to form bone-facing ruffled borders enriched in lysosomal membrane proteins. It remains elusi...
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doaj-7c4230d63c964233a8729fadeb3fa3102020-11-24T21:24:59ZengElsevieriScience2589-00422018-08-016199211ARAP1 Bridges Actin Dynamics and AP-3-Dependent Membrane Traffic in Bone-Digesting OsteoclastsSandra Segeletz0Lydia Danglot1Thierry Galli2Bernard Hoflack3Biotechnology Center, Technische Universität Dresden, Tatzberg 47-51, Dresden 01307, GermanyCentre de Psychiatrie et Neurosciences, UMR-S894 INSERM, Université Paris Descartes, 102-108 rue de la Santé, Paris 75014, FranceCentre de Psychiatrie et Neurosciences, UMR-S894 INSERM, Université Paris Descartes, 102-108 rue de la Santé, Paris 75014, FranceBiotechnology Center, Technische Universität Dresden, Tatzberg 47-51, Dresden 01307, Germany; Corresponding authorSummary: Bone-resorbing osteoclasts play a central role in bone remodeling and its pathology. To digest bone, osteoclasts re-organize both F-actin, to assemble podosomes/sealing zones, and membrane traffic, to form bone-facing ruffled borders enriched in lysosomal membrane proteins. It remains elusive how these processes are coordinated. Here, we show that ARAP1 (ArfGAP with RhoGAP domain, ankyrin repeat and PH domain-containing protein 1) fulfills this function. At podosomes/sealing zones, ARAP1 is part of a protein complex where its RhoGAP domain regulates actin dynamics. At endosomes, ARAP1 interacts with AP-3 adaptor complexes where its Arf-GAP domain regulates the Arf1-dependent AP-3 binding to membranes and, consequently lysosomal membrane protein transport to ruffled borders. Accordingly, ARAP1 or AP-3 depletion in osteoclasts alters their capacity to digest bone in vitro. and AP-3δ-deficient mocha mice, a model of the Hermansky-Pudlak storage pool syndrome, develop osteoporosis. Thus, ARAP1 bridges F-actin and membrane dynamics in osteoclasts for proper bone homeostasis. : Cell Biology; Organizational Aspects of Cell Biology; Functional Aspects of Cell Biology Subject Areas: Cell Biology, Organizational Aspects of Cell Biology, Functional Aspects of Cell Biologyhttp://www.sciencedirect.com/science/article/pii/S258900421830107X |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sandra Segeletz Lydia Danglot Thierry Galli Bernard Hoflack |
spellingShingle |
Sandra Segeletz Lydia Danglot Thierry Galli Bernard Hoflack ARAP1 Bridges Actin Dynamics and AP-3-Dependent Membrane Traffic in Bone-Digesting Osteoclasts iScience |
author_facet |
Sandra Segeletz Lydia Danglot Thierry Galli Bernard Hoflack |
author_sort |
Sandra Segeletz |
title |
ARAP1 Bridges Actin Dynamics and AP-3-Dependent Membrane Traffic in Bone-Digesting Osteoclasts |
title_short |
ARAP1 Bridges Actin Dynamics and AP-3-Dependent Membrane Traffic in Bone-Digesting Osteoclasts |
title_full |
ARAP1 Bridges Actin Dynamics and AP-3-Dependent Membrane Traffic in Bone-Digesting Osteoclasts |
title_fullStr |
ARAP1 Bridges Actin Dynamics and AP-3-Dependent Membrane Traffic in Bone-Digesting Osteoclasts |
title_full_unstemmed |
ARAP1 Bridges Actin Dynamics and AP-3-Dependent Membrane Traffic in Bone-Digesting Osteoclasts |
title_sort |
arap1 bridges actin dynamics and ap-3-dependent membrane traffic in bone-digesting osteoclasts |
publisher |
Elsevier |
series |
iScience |
issn |
2589-0042 |
publishDate |
2018-08-01 |
description |
Summary: Bone-resorbing osteoclasts play a central role in bone remodeling and its pathology. To digest bone, osteoclasts re-organize both F-actin, to assemble podosomes/sealing zones, and membrane traffic, to form bone-facing ruffled borders enriched in lysosomal membrane proteins. It remains elusive how these processes are coordinated. Here, we show that ARAP1 (ArfGAP with RhoGAP domain, ankyrin repeat and PH domain-containing protein 1) fulfills this function. At podosomes/sealing zones, ARAP1 is part of a protein complex where its RhoGAP domain regulates actin dynamics. At endosomes, ARAP1 interacts with AP-3 adaptor complexes where its Arf-GAP domain regulates the Arf1-dependent AP-3 binding to membranes and, consequently lysosomal membrane protein transport to ruffled borders. Accordingly, ARAP1 or AP-3 depletion in osteoclasts alters their capacity to digest bone in vitro. and AP-3δ-deficient mocha mice, a model of the Hermansky-Pudlak storage pool syndrome, develop osteoporosis. Thus, ARAP1 bridges F-actin and membrane dynamics in osteoclasts for proper bone homeostasis. : Cell Biology; Organizational Aspects of Cell Biology; Functional Aspects of Cell Biology Subject Areas: Cell Biology, Organizational Aspects of Cell Biology, Functional Aspects of Cell Biology |
url |
http://www.sciencedirect.com/science/article/pii/S258900421830107X |
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