Activation of ROCK by RhoA is regulated by cell adhesion, shape, and cytoskeletal tension

Bhadriraju, Kiran; Yang, Michael T.; Ruiz, Sami Alom; Pirone, Dana M.; Tan, John L.; Chen, Christopher

doi:10.1016/j.yexcr.2007.07.002

Cited by 222 publications

(204 citation statements)

References 31 publications

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“…The observed increase in cell spreading ( Fig. 2A,B) fits well with a decrease in actomyosin contractility, because MRLC needs to be downregulated to allow cell spreading, either through the RhoA-ROCK pathway (Arthur and Burridge, 2001;Arthur et al, 2000;Bhadriraju et al, 2007) or through MLCK (Takizawa et al, 2007). Contractility is also required for the positioning of the nucleus during directed cell migration (Gomes et al, 2005), and a decrease concurs with the observed decrease in orientation of the Golgi towards the wound.…”

Section: Escrts Positively Regulate Myosin Light Chain Functions Throsupporting

confidence: 69%

The ESCRT machinery mediates polarization of fibroblasts through regulation of myosin light chain

Lobert

Stenmark

2012

Journal of Cell Science

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SummaryRecent evidence implicates the endosomal sorting complex required for transport (ESCRT) in the regulation of epithelial polarity in Drosophila melanogaster, but the mechanisms responsible for this action remain unclear. Here we show that ESCRTs determine cell orientation during directed migration in human fibroblasts. We find that endosomal retention of a5b1 integrin and its downstream signaling effector Src in ESCRT-depleted cells is accompanied by the failure to activate myosin light chain kinase (MLCK), which thereby cannot phosphorylate myosin regulatory light chain (MRLC). Using this mechanism, ESCRT-depleted fibroblasts fail to orient their Golgi complex to undergo directional migration and show impaired focal adhesion turnover and increased spreading on fibronectin. Consistent with these findings, expression of a phosphomimetic mutant of MRLC in ESCRT-depleted cells restores normal phenotypes during cell spreading and orientation of the Golgi. These results suggest that, through their role in regulating integrin trafficking, ESCRTs regulate phosphorylation of MRLC and, subsequently, Golgi orientation and cell spreading.

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Section: Escrts Positively Regulate Myosin Light Chain Functions Throsupporting

confidence: 69%

The ESCRT machinery mediates polarization of fibroblasts through regulation of myosin light chain

Lobert

Stenmark

2012

Journal of Cell Science

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“…Cells restrained in their spreading for instance display high RhoA but low ROCK activity (Bhadriraju et al, 2007). This suggests that mechanical properties of the substratum may impinge on RhoA signaling by preventing or restricting binding of the GTPase to a subset of downstream effectors.…”

Section: Discussionmentioning

confidence: 99%

Rho GTPases in osteoclasts: Orchestrators of podosome arrangement

Ory

Brazier

Pawlak

et al. 2008

European Journal of Cell Biology

130

101

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Cells from the myeloid lineage, namely macrophages, dendritic cells and osteoclasts develop podosomes instead of stress fibers and focal adhesions to adhere and migrate.Podosomes share many components with focal adhesions but differ in their molecular organization, with a dense core of polymerized actin surrounded by scaffolding proteins, kinases and integrins. Podosomes are found either isolated both in macrophages and dendritic cells or arranged into superstructures in osteoclasts. When osteoclasts resorb bone, they form an F-actin rich sealing zone, which is a dense array of connected podosomes that firmly anchors osteoclasts to bone. It delineates a compartment in which protons and proteases are secreted to dissolve and degrade the mineralized matrix. Since Rho GTPases have been shown to control F-actin stress fibers and focal adhesions in mesenchymal cells, the question of whether they could also control podosome formation and arrangement in cells from the myeloid lineage, and particularly in osteoclasts, rapidly emerged. This article considers recent advances made in our understanding of podosome arrangements in osteoclasts and how Rho GTPases may control it.

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“…Stretch applied on a cell due to external mechanical force or attachment to the stiffer substrates affects actin near the adhesion site and is followed by recruitment of adhesion complex proteins and global cytoskeletal rearrangements (Galbraith et al, 2002;Riveline et al, 2001). Multiple actinbinding proteins at the cell adhesion sites directly respond to substrate rigidity (overviewed in Dobereiner et al, 2005), resulting in changes to all steps of the migration cycle and all of the structural and signaling molecules involved (Beningo et al, 2004;Bhadriraju et al, 2007;Gunzer et al, 2000;Knight et al, 2000).…”

Section: Extracellular Matrix and Force Sensing: Paving The Pathways mentioning

confidence: 99%

Cell biology of embryonic migration

Kurosaka¹,

Kashina²

2008

Birth Defects Research Pt C

113

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Cell migration is an evolutionarily conserved mechanism that underlies the development and functioning of uni-and multicellular organisms and takes place in normal and pathogenic processes, including various events of embryogenesis, wound healing, immune response, cancer metastases, and angiogenesis. Despite the differences in the cell types that take part in different migratory events, it is believed that all of these migrations occur by similar molecular mechanisms, whose major components have been functionally conserved in evolution and whose perturbation leads to severe developmental defects. These mechanisms involve intricate cytoskeleton-based molecular machines that can sense the environment, respond to signals, and modulate the entire cell behavior. A big question that has concerned the researchers for decades relates to the coordination of cell migration in situ and its relation to the intracellular aspects of the cell migratory mechanisms. Traditionally, this question has been addressed by researchers that considered the intra-and extracellular mechanisms driving migration in separate sets of studies. As more data accumulate researchers are now able to integrate all of the available information and consider the intracellular mechanisms of cell migration in the context of the developing organisms that contain additional levels of complexity provided by extracellular regulation. This review provides a broad summary of the existing and emerging data in the cell and developmental biology fields regarding cell migration during development.

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Activation of ROCK by RhoA is regulated by cell adhesion, shape, and cytoskeletal tension

Cited by 222 publications

References 31 publications

The ESCRT machinery mediates polarization of fibroblasts through regulation of myosin light chain

The ESCRT machinery mediates polarization of fibroblasts through regulation of myosin light chain

Rho GTPases in osteoclasts: Orchestrators of podosome arrangement

Cell biology of embryonic migration

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