Coordination by Cdc42 of Actin, Contractility, and Adhesion for Melanoblast Movement in Mouse Skin.

2.50
Hdl Handle:
http://hdl.handle.net/10033/620889
Title:
Coordination by Cdc42 of Actin, Contractility, and Adhesion for Melanoblast Movement in Mouse Skin.
Authors:
Woodham, Emma F; Paul, Nikki R; Tyrrell, Benjamin; Spence, Heather J; Swaminathan, Karthic; Scribner, Michelle R; Giampazolias, Evangelos; Hedley, Ann; Clark, William; Kage, Frieda; Marston, Daniel J; Hahn, Klaus M; Tait, Stephen W G; Larue, Lionel; Brakebusch, Cord H; Insall, Robert H; Machesky, Laura M
Abstract:
The individual molecular pathways downstream of Cdc42, Rac, and Rho GTPases are well documented, but we know surprisingly little about how these pathways are coordinated when cells move in a complex environment in vivo. In the developing embryo, melanoblasts originating from the neural crest must traverse the dermis to reach the epidermis of the skin and hair follicles. We previously established that Rac1 signals via Scar/WAVE and Arp2/3 to effect pseudopod extension and migration of melanoblasts in skin. Here we show that RhoA is redundant in the melanocyte lineage but that Cdc42 coordinates multiple motility systems independent of Rac1. Similar to Rac1 knockouts, Cdc42 null mice displayed a severe loss of pigmentation, and melanoblasts showed cell-cycle progression, migration, and cytokinesis defects. However, unlike Rac1 knockouts, Cdc42 null melanoblasts were elongated and displayed large, bulky pseudopods with dynamic actin bursts. Despite assuming an elongated shape usually associated with fast mesenchymal motility, Cdc42 knockout melanoblasts migrated slowly and inefficiently in the epidermis, with nearly static pseudopods. Although much of the basic actin machinery was intact, Cdc42 null cells lacked the ability to polarize their Golgi and coordinate motility systems for efficient movement. Loss of Cdc42 de-coupled three main systems: actin assembly via the formin FMNL2 and Arp2/3, active myosin-II localization, and integrin-based adhesion dynamics.
Affiliation:
Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
Citation:
Coordination by Cdc42 of Actin, Contractility, and Adhesion for Melanoblast Movement in Mouse Skin. 2017, 27 (5):624-637 Curr. Biol.
Journal:
Current biology : CB
Issue Date:
6-Mar-2017
URI:
http://hdl.handle.net/10033/620889
DOI:
10.1016/j.cub.2017.01.033
PubMed ID:
28238662
Type:
Article
Language:
en
ISSN:
1879-0445
Appears in Collections:
publications of the Research group: molecular cell biology (MZBI)

Full metadata record

DC FieldValue Language
dc.contributor.authorWoodham, Emma Fen
dc.contributor.authorPaul, Nikki Ren
dc.contributor.authorTyrrell, Benjaminen
dc.contributor.authorSpence, Heather Jen
dc.contributor.authorSwaminathan, Karthicen
dc.contributor.authorScribner, Michelle Ren
dc.contributor.authorGiampazolias, Evangelosen
dc.contributor.authorHedley, Annen
dc.contributor.authorClark, Williamen
dc.contributor.authorKage, Friedaen
dc.contributor.authorMarston, Daniel Jen
dc.contributor.authorHahn, Klaus Men
dc.contributor.authorTait, Stephen W Gen
dc.contributor.authorLarue, Lionelen
dc.contributor.authorBrakebusch, Cord Hen
dc.contributor.authorInsall, Robert Hen
dc.contributor.authorMachesky, Laura Men
dc.date.accessioned2017-04-07T08:25:19Z-
dc.date.available2017-04-07T08:25:19Z-
dc.date.issued2017-03-06-
dc.identifier.citationCoordination by Cdc42 of Actin, Contractility, and Adhesion for Melanoblast Movement in Mouse Skin. 2017, 27 (5):624-637 Curr. Biol.en
dc.identifier.issn1879-0445-
dc.identifier.pmid28238662-
dc.identifier.doi10.1016/j.cub.2017.01.033-
dc.identifier.urihttp://hdl.handle.net/10033/620889-
dc.description.abstractThe individual molecular pathways downstream of Cdc42, Rac, and Rho GTPases are well documented, but we know surprisingly little about how these pathways are coordinated when cells move in a complex environment in vivo. In the developing embryo, melanoblasts originating from the neural crest must traverse the dermis to reach the epidermis of the skin and hair follicles. We previously established that Rac1 signals via Scar/WAVE and Arp2/3 to effect pseudopod extension and migration of melanoblasts in skin. Here we show that RhoA is redundant in the melanocyte lineage but that Cdc42 coordinates multiple motility systems independent of Rac1. Similar to Rac1 knockouts, Cdc42 null mice displayed a severe loss of pigmentation, and melanoblasts showed cell-cycle progression, migration, and cytokinesis defects. However, unlike Rac1 knockouts, Cdc42 null melanoblasts were elongated and displayed large, bulky pseudopods with dynamic actin bursts. Despite assuming an elongated shape usually associated with fast mesenchymal motility, Cdc42 knockout melanoblasts migrated slowly and inefficiently in the epidermis, with nearly static pseudopods. Although much of the basic actin machinery was intact, Cdc42 null cells lacked the ability to polarize their Golgi and coordinate motility systems for efficient movement. Loss of Cdc42 de-coupled three main systems: actin assembly via the formin FMNL2 and Arp2/3, active myosin-II localization, and integrin-based adhesion dynamics.en
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleCoordination by Cdc42 of Actin, Contractility, and Adhesion for Melanoblast Movement in Mouse Skin.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.en
dc.identifier.journalCurrent biology : CBen

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