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Rho GTPases in ameloblast differentiation

View Article: PubMed Central - PubMed

ABSTRACT

During tooth development, ameloblasts differentiate from inner enamel epithelial cells to enamel-forming cells by modulating the signal pathways mediating epithelial–mesenchymal interaction and a cell-autonomous gene network. The differentiation process of epithelial cells is characterized by marked changes in their morphology and polarity, accompanied by dynamic cytoskeletal reorganization and changes in cell–cell and cell–matrix adhesion over time. Functional ameloblasts are tall, columnar, polarized cells that synthesize and secrete enamel-specific proteins. After deposition of the full thickness of enamel matrix, ameloblasts become smaller and regulate enamel maturation. Recent significant advances in the fields of molecular biology and genetics have improved our understanding of the regulatory mechanism of the ameloblast cell life cycle, mediated by the Rho family of small GTPases. They act as intracellular molecular switch that transduce signals from extracellular stimuli to the actin cytoskeleton and the nucleus. In our review, we summarize studies that provide current evidence for Rho GTPases and their involvement in ameloblast differentiation. In addition to the Rho GTPases themselves, their downstream effectors and upstream regulators have also been implicated in ameloblast differentiation.

No MeSH data available.


The molecular structure of ROCK. ROCK sequences include a kinase domain located at the amino terminus of the protein, a coiled-coil region containing RBD, and a PH domain with a cysteine-rich domain (CRD). ROCK I and ROCK II are highly homologous, with an overall amino acid sequence identity of 65% (A). Intramolecular association of the C-terminal region and the kinase domain. Rho binding induces conformational changes that inhibit its ability to promote kinase activation (B).
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fig0015: The molecular structure of ROCK. ROCK sequences include a kinase domain located at the amino terminus of the protein, a coiled-coil region containing RBD, and a PH domain with a cysteine-rich domain (CRD). ROCK I and ROCK II are highly homologous, with an overall amino acid sequence identity of 65% (A). Intramolecular association of the C-terminal region and the kinase domain. Rho binding induces conformational changes that inhibit its ability to promote kinase activation (B).

Mentions: The effects of Rho GTPases on a wide variety of cellular events are mediated by the stimulation of downstream effector kinases by activated Rho GTPases. Among RhoA effectors, the most well-known proteins are Rho kinase (ROCK) and mammalian diaphanous (mDia) (Fig. 2). ROCK is a serine/threonine kinase with a molecular mass of approximately 160 kDa. Two distinct genes encode two isoforms: ROCK I (p160-ROCK, ROKβ) and ROCK II (Rho kinase and ROKα) [58], [59], [60] (Fig. 3). The human ROCK I and ROCK II genes are located on chromosome 18 (18q11.1) and chromosome 2 (2P24), respectively. These isoforms are highly homologous, with an overall amino acid sequence identity of 65%. Their homology reaches 90% in the N-terminal serine/threonine kinase domains, with lower identity in their C-terminal [60]. Both isoforms consist of N-terminal kinase domains, a central coiled-coil region containing the Rho binding domain (RBD), and a C-terminal PH domain with a Cys-rich region. The C-terminus, including the RBD and PH domains, is an auto-inhibitory region that inhibits kinase activity under basal conditions via intramolecular association with the kinase domain [61], [62]. Rho proteins bind to the ROCK RBD domain in their active GTP-charged state, which enhances ROCK catalytic activity through induction of conformational changes that diminish C-terminal-mediated auto-inhibition via exposure of the kinase domain [59], [62], [63], [64] (Fig. 3).


Rho GTPases in ameloblast differentiation
The molecular structure of ROCK. ROCK sequences include a kinase domain located at the amino terminus of the protein, a coiled-coil region containing RBD, and a PH domain with a cysteine-rich domain (CRD). ROCK I and ROCK II are highly homologous, with an overall amino acid sequence identity of 65% (A). Intramolecular association of the C-terminal region and the kinase domain. Rho binding induces conformational changes that inhibit its ability to promote kinase activation (B).
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC5382790&req=5

fig0015: The molecular structure of ROCK. ROCK sequences include a kinase domain located at the amino terminus of the protein, a coiled-coil region containing RBD, and a PH domain with a cysteine-rich domain (CRD). ROCK I and ROCK II are highly homologous, with an overall amino acid sequence identity of 65% (A). Intramolecular association of the C-terminal region and the kinase domain. Rho binding induces conformational changes that inhibit its ability to promote kinase activation (B).
Mentions: The effects of Rho GTPases on a wide variety of cellular events are mediated by the stimulation of downstream effector kinases by activated Rho GTPases. Among RhoA effectors, the most well-known proteins are Rho kinase (ROCK) and mammalian diaphanous (mDia) (Fig. 2). ROCK is a serine/threonine kinase with a molecular mass of approximately 160 kDa. Two distinct genes encode two isoforms: ROCK I (p160-ROCK, ROKβ) and ROCK II (Rho kinase and ROKα) [58], [59], [60] (Fig. 3). The human ROCK I and ROCK II genes are located on chromosome 18 (18q11.1) and chromosome 2 (2P24), respectively. These isoforms are highly homologous, with an overall amino acid sequence identity of 65%. Their homology reaches 90% in the N-terminal serine/threonine kinase domains, with lower identity in their C-terminal [60]. Both isoforms consist of N-terminal kinase domains, a central coiled-coil region containing the Rho binding domain (RBD), and a C-terminal PH domain with a Cys-rich region. The C-terminus, including the RBD and PH domains, is an auto-inhibitory region that inhibits kinase activity under basal conditions via intramolecular association with the kinase domain [61], [62]. Rho proteins bind to the ROCK RBD domain in their active GTP-charged state, which enhances ROCK catalytic activity through induction of conformational changes that diminish C-terminal-mediated auto-inhibition via exposure of the kinase domain [59], [62], [63], [64] (Fig. 3).

View Article: PubMed Central - PubMed

ABSTRACT

During tooth development, ameloblasts differentiate from inner enamel epithelial cells to enamel-forming cells by modulating the signal pathways mediating epithelial–mesenchymal interaction and a cell-autonomous gene network. The differentiation process of epithelial cells is characterized by marked changes in their morphology and polarity, accompanied by dynamic cytoskeletal reorganization and changes in cell–cell and cell–matrix adhesion over time. Functional ameloblasts are tall, columnar, polarized cells that synthesize and secrete enamel-specific proteins. After deposition of the full thickness of enamel matrix, ameloblasts become smaller and regulate enamel maturation. Recent significant advances in the fields of molecular biology and genetics have improved our understanding of the regulatory mechanism of the ameloblast cell life cycle, mediated by the Rho family of small GTPases. They act as intracellular molecular switch that transduce signals from extracellular stimuli to the actin cytoskeleton and the nucleus. In our review, we summarize studies that provide current evidence for Rho GTPases and their involvement in ameloblast differentiation. In addition to the Rho GTPases themselves, their downstream effectors and upstream regulators have also been implicated in ameloblast differentiation.

No MeSH data available.