[5] While the effects of RhoA activity are not all well known, it is primarily associated with cytoskeleton regulation, mostly actin stress fibers formation and actomyosin contractility.
Both of these switches have characteristic folding, correspond to specific regions on the RhoA coil and are uniformly stabilized via hydrogen bonds.
The nature of the bound nucleotide and the ensuing conformational modification of the Switch domains dictates the ability of RhoA to bind or not with partner proteins (see below).
The C-terminal of RhoA is modified via prenylation, anchoring the GTPase into membranes, which is essential for its role in cell growth and cytoskeleton organization.
RhoA is sequestered by dissociation inhibitors (RhoGDIs) which remove the protein from the membrane while preventing its further interaction with other downstream effectors.
Signal transduction pathways regulated via RhoA link plasma membrane receptors to focal adhesion formation and the subsequent activation of relevant actin stress fibers.
ROCK kinases induce actomyosin-based contractility and phosphorylate TAU and MAP2 involved in regulating myosins and other actin-binding proteins in order to assist in cell migration and detachment.
RhoA also regulates the integrity of the extracellular matrix and the loss of corresponding cell-cell adhesions (primarily adherens and tight junctions) required for the migration of epithelial.
RhoA is required for processes involving cell development, some of which include outgrowth, dorsal closure, bone formation, and myogenesis.
In extension, RhoA has been shown to function as an intermediary switch within the overall mechanically mediated process of stem cell commitment and differentiation.
[11] Transforming growth factor (TGF)-mediated pathways that control tumor progression and identity are also frequently noted to be RhoA-dependent mechanisms.
RhoA plays a pivotal role in G1 cell cycle progression, primarily through regulation of cyclin D1 and cyclin-dependent kinase inhibitors (p21 and p27) expression.
[16][17][18][19] After global ischemia, hyperbaric oxygen (at least at 3 ATA) appears to partially suppress expression of RhoA, in addition to Nogo protein (Reticulon 4), and a subunit of its receptor Ng-R.[20] The MEMO1-RhoA-DIAPH1 signaling pathway plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex.
Ras homolog family member A (RhoA) causes the actin cytoskeleton to become rigid which limits growth cone mobility and inhibits neuronal elongation in the developing nervous system.
In addition to promoting tumor-suppression activity, RhoA also has inherent impact upon the efficacy of drugs in relation to cancer functionality and could be applied to gene therapy protocols in future research.
[64] Protein expression of RhoA has been identified to be significantly higher in testicular tumor tissue than that in nontumor tissue; expression of protein for RhoA, ROCK-I, ROCK-II, Rac1, and Cdc42 was greater in tumors of higher stages than lower stages, coinciding with greater lymph metastasis and invasion in upper urinary tract cancer.
Although both RhoA and RhoC proteins comprise a significant part of the Rho GTPases that are linked to promoting the invasive behavior of breast carcinomas, attributing specific functions to these individual members has been difficult.
Due to differences proteins exhibited between normal and affected neutrocytes, RhoA has become the key element; further experimentation has also shown that RhoA-inhibiting pathways prevent the overall growth of CML cells.
[66] RhoA's physiological functions have been linked to the contraction and migration of cells which are manifested as symptoms in both asthma and diabetes (i.e. airflow limitation and hyper-responsiveness, desensitization, etc.).