Rho Kinases in Embryonic Development and Stem Cell Research

Abstract

The Rho-associated coiled-coil containing kinases (ROCKs or Rho kinases) belong to the AGC (PKA/PKG/PKC) family of serine/threonine kinases and are major downstream effectors of small GTPase RhoA, a key regulator of actin-cytoskeleton reorganization. The ROCK family contains two members, ROCK1 and ROCK2, which share 65% overall identity and 92% identity in kinase domain. ROCK1 and ROCK2 were assumed to be functionally redundant, based largely on their major common activators, their high degree kinase domain homology, and study results from overexpression with kinase constructs or chemical inhibitors. ROCK signaling research has expanded to all areas of biology and medicine since its discovery in 1996. The rapid advance is befitting ROCK’s versatile functions in modulating various cell behavior, such as contraction, adhesion, migration, proliferation, polarity, cytokinesis, and differentiation. The rapid advance is noticeably driven by an extensive linking with clinical medicine, including cardiovascular abnormalities, aberrant immune responsive, and cancer development and metastasis. The rapid advance during the past decade is further powered by novel biotechnologies including CRISPR-Cas and single cell omics. Current consensus, derived mainly from gene targeting and RNA interference approaches, is that the two ROCK isoforms have overlapping and distinct cellular, physiological and pathophysiology roles. In this review, we present an overview of the milestone discoveries in ROCK research. We then focus on the current understanding of ROCK signaling in embryonic development, current research status using knockout and knockin mouse models, and stem cell research.

Polystyrene Nanoplastics Activate Autophagy and Suppress Trophoblast Cell Migration/Invasion and Migrasome Formation to Induce Miscarriage

“…Most of these genes were altered in PS-NP-exposed trophoblast cells, among which the Rho-ROCK pathway exhibited significant changes (Figure A,B). The ROCK family contains two members, ROCK1 and ROCK2, both of which share high sequence identity in the kinase domain and contribute to multiple cytoskeletal functions . Experiments confirmed that the mRNA and protein levels of ROCK1 were all reduced with increasing PS-NP concentrations in PS-NP-exposed trophoblast cells (Figure C–E).…”

Heimdall, an alternative protein issued from a ncRNA related to kappa light chain variable region of immunoglobulins from astrocytes: a new player in neural proteome

“…We also performed this proteomic analysis under LPS treatment and exclusive proteins identified in Heimdall KO were related to axon guidance such as the receptor Plexin C1 [ 72 ], Pdgfrb [ 73 ], Collapsin response mediator protein 1 [ 74 ], Brk1 [ 75 ], Glioblastoma amplified sequence [ 76 ], Prosaposin [ 77 ], Retinoblastoma binding protein 6 [ 78 ], Thrombospondin 1 [ 79 ], Rho-associated coiled-coil containing protein kinase 1 [ 80 ], and interferon-related developmental regulator 2 (Supp. Data 11 ).…”

Acrolein, an endogenous aldehyde induces synaptic dysfunction in vitro and in vivo: Involvement of RhoA/ROCK2 pathway

“…After ROCK is activated by Rho, the actin‐binding protein cofilin is abnormally phosphorylate and loses the function of cutting actin (Guiler et al, 2021 ). ROCKs have more than 30 downstream substrates, the most classic ones include Tau, Limk1, and p‐cofilin, etc (Shi & Wei, 2022 ). Inhibition of RhoA/ROCK2/Limk1/cofilin signaling pathway rescued the memory impairments and synaptic disorder in AD rat (Han et al, 2020 ).…”