Regulation of smooth muscle contraction by monomeric non‐RhoA GTPases

Abstract

Smooth muscle contraction in the cardiovascular system, airways, prostate and lower urinary tract is involved in the pathophysiology of many diseases, including cardiovascular and obstructive lung disease plus lower urinary tract symptoms, which are associated with high prevalence of morbidity and mortality. This prominent clinical role of smooth muscle tone has led to the molecular mechanisms involved being subjected to extensive research. In general smooth muscle contraction is promoted by three major signalling pathways, including the monomeric GTPase RhoA pathway. However, emerging evidence suggests that monomeric GTPases other than RhoA may be involved in signal transduction in smooth muscle contraction, including Rac GTPases, cell division control protein 42 homologue, adenosine ribosylation factor 6, Ras, Rap1b and Rab GTPases. Here, we review these emerging functions of non‐RhoA GTPases in smooth muscle contraction, which has now become increasingly more evident and constitutes an emerging and innovative research area of high clinical relevance.

ADP Ribosylation Factor 6 Promotes Contraction and Proliferation, Suppresses Apoptosis and Is Specifically Inhibited by NAV2729 in Prostate Stromal Cells

“…A role of ARF6 in prostate smooth muscle contraction is in line with analog functions of other monomeric GTPases in smooth muscle contraction, which are emerging or already wellestablished (Li et al, 2020b). RhoA-mediated smooth muscle contraction is widely accepted and proven for probably any smooth muscle type (Somlyo and Somlyo, 2003).…”

“…More recently, similar roles in smooth muscle contraction have been proposed for other monomeric GTPases (Li et al, 2020b). In particular for Rac GTPases, a role in smooth muscle contraction in different organs becomes increasingly obvious (Li et al, 2020b). Other non-RhoA GTPases with supposed roles in regulation of smooth muscle contraction include RasGTPases, Rap1b, Rab11A, Rab35, and Cdc42 (Li et al, 2020b).…”

“…RhoA-mediated smooth muscle contraction is widely accepted and proven for probably any smooth muscle type (Somlyo and Somlyo, 2003). More recently, similar roles in smooth muscle contraction have been proposed for other monomeric GTPases (Li et al, 2020b). In particular for Rac GTPases, a role in smooth muscle contraction in different organs becomes increasingly obvious (Li et al, 2020b).…”

“…In particular for Rac GTPases, a role in smooth muscle contraction in different organs becomes increasingly obvious (Li et al, 2020b). Other non-RhoA GTPases with supposed roles in regulation of smooth muscle contraction include RasGTPases, Rap1b, Rab11A, Rab35, and Cdc42 (Li et al, 2020b). It may be speculated, that promotion of smooth muscle contraction by ARF6 is not limited to prostate smooth This article has not been copyedited and formatted.…”

“…RhoA-mediated contraction and proliferation of smooth muscle cells has been confirmed for all types of smooth muscle and is widely accepted (Somlyo and Somlyo, 2003). Similar roles of other monomeric GTPases in smooth muscle contraction of different smooth muscle-rich organs are an emerging field (Li et al, 2020a). Considering that widespread diseases including arterial hypertension or obstructive airway diseases are related to abberrant smooth muscle contraction, proving a This article has not been copyedited and formatted.…”