Rho GTPases are essential regulators of the actin cytoskeleton.They are involved in various physiological and biochemical processes such as the regulation of cytoskeleton dynamics,development,proliferation,survival,an...Rho GTPases are essential regulators of the actin cytoskeleton.They are involved in various physiological and biochemical processes such as the regulation of cytoskeleton dynamics,development,proliferation,survival,and regeneration.During the development of cochlear hair cells,Rho GTPases are activated by various extracellular signals through membrane receptors to further stimulate multiple downstream effectors.Specifically,RhoA,Cdc42,and Rac1,members of the classical subfamily of the Rho GTPase family,regulate the development and maintenance of cilia by inducing the polymerization of actin monomers and stabilizing actin filaments.In addition,they also regulate the normal morphology orientation of ciliary bundles in auditory hair cells,which is an important element of cell polarity regulation.Moreover,the actin-related pathways mediated by RhoA,Cdc42,and Rac1 also play a role in the motility of outer hair cells,indicating that the function of Rho GTPases is crucial in the highly polar auditory sensory system.In this review,we focus on the expression of RhoA,Cdc42,and Rac1 in cochlear hair cells and how these small molecules participate in ciliary bundle morphogenesis and cochlear hair cell movement.We also discuss the progress of current research investigating the use of these small molecules as drug targets for deafness treatment.展开更多
BACKGROUND： Rho GTPase family members have been shown to participate in neurite growth by regulating the neuronal cytoskeleton. However, there are very few reports of developmental roles of signaling molecules relate...BACKGROUND： Rho GTPase family members have been shown to participate in neurite growth by regulating the neuronal cytoskeleton. However, there are very few reports of developmental roles of signaling molecules related to Rho GTPases. OBJECTIVE： To investigate messenger ribonucleic acid mRNA expression of signaling molecules associated with Rho GTPases, including Rho-A, Rac-1, collapsin response mediator protein 1 （CRMP-1）, and tubulin 133 （Tub/33） during rat hippocampus development. DESIGN, TIME AND SETTING- A non-randomized, controlled, animal experiment, based on different developmental stages of the rat hippocampus, was performed at the Guangdong Key Laboratory of Tissue Construction and Detection, Institute of Clinical Anatomy, Southern Medical University between December 2005 and July 2007. MATERIALS： Trizol reagent was purchased from Invitrogen, USA. RNA PCR kit （AMV） Ver 3.0 and 150 bp DNA Ladder Marker were purchased from TaKaRa, Japan. Unless otherwise specified, all other reagents were purchased from Sigma-Aldrich, USA. METHODS： Twenty-five Sprague Dawley rats were assigned to five groups （n = 5） according to developmental stages： embryonic （embryonic 15 days）, neonatal （postnatal 5 days）, juvenile （postnatal 1 month）, adult （postnatal 3 months）, and senile （postnatal 18 months）. MAIN OUTCOME MEASURES： Detection of mRNA expression of Rho-A, Rac-1, CRMP-1, and Tub β3 during various hippocampal developmental stages by reverse-transcription polymerase chain reaction. RESULTS： Hippocampal mRNA expression of Rho-A, as well as Rac-1, reached peak levels at embryonic, juvenile, and senile stages, and was relatively less during neonatal and adult stages. mRNA expression of Rac-1 was greater than Rho-A during each hippocampal developmental stage. CRMP-1 mRNA expression levels were as follows： embryonic 〉 neonatal 〉 juvenile 〉 adult 〈 senile, while Tubβ3 mRNA expression was embryonic 〉 neonatal 〉 juvenile 〉 adult = senile. CONCLUSION： Rho-A and Rac-1 shared similar expression profiles, which demonstrated similar variations during the entire rat hippocampus developmental process. However, Rac-1 mRNA expression remained greater than Rho-A. Both CRMP-1 and Tubβ3 mRNA expression profiles gradually declined during hippocampal development from embryonic to adult stages. Tubβ3 mRNA expression arrested during the adult stage, and CRMP-1 mRNA expression increased during the senile stage.展开更多
基金supported by the Natural Science Foundation of Jiangsu Province,No.BK20221377(to JG)the Natural Science Foundation of the Jiangsu Higher Education Institutions of China,No.22KJB180023(to JG)。
文摘Rho GTPases are essential regulators of the actin cytoskeleton.They are involved in various physiological and biochemical processes such as the regulation of cytoskeleton dynamics,development,proliferation,survival,and regeneration.During the development of cochlear hair cells,Rho GTPases are activated by various extracellular signals through membrane receptors to further stimulate multiple downstream effectors.Specifically,RhoA,Cdc42,and Rac1,members of the classical subfamily of the Rho GTPase family,regulate the development and maintenance of cilia by inducing the polymerization of actin monomers and stabilizing actin filaments.In addition,they also regulate the normal morphology orientation of ciliary bundles in auditory hair cells,which is an important element of cell polarity regulation.Moreover,the actin-related pathways mediated by RhoA,Cdc42,and Rac1 also play a role in the motility of outer hair cells,indicating that the function of Rho GTPases is crucial in the highly polar auditory sensory system.In this review,we focus on the expression of RhoA,Cdc42,and Rac1 in cochlear hair cells and how these small molecules participate in ciliary bundle morphogenesis and cochlear hair cell movement.We also discuss the progress of current research investigating the use of these small molecules as drug targets for deafness treatment.
基金Supported by:the National Basic Research Program of China(973 Program),No. 2007CB512705the Natural Science Foundation of Guangdong Province,No. 8451063201000193
文摘BACKGROUND： Rho GTPase family members have been shown to participate in neurite growth by regulating the neuronal cytoskeleton. However, there are very few reports of developmental roles of signaling molecules related to Rho GTPases. OBJECTIVE： To investigate messenger ribonucleic acid mRNA expression of signaling molecules associated with Rho GTPases, including Rho-A, Rac-1, collapsin response mediator protein 1 （CRMP-1）, and tubulin 133 （Tub/33） during rat hippocampus development. DESIGN, TIME AND SETTING- A non-randomized, controlled, animal experiment, based on different developmental stages of the rat hippocampus, was performed at the Guangdong Key Laboratory of Tissue Construction and Detection, Institute of Clinical Anatomy, Southern Medical University between December 2005 and July 2007. MATERIALS： Trizol reagent was purchased from Invitrogen, USA. RNA PCR kit （AMV） Ver 3.0 and 150 bp DNA Ladder Marker were purchased from TaKaRa, Japan. Unless otherwise specified, all other reagents were purchased from Sigma-Aldrich, USA. METHODS： Twenty-five Sprague Dawley rats were assigned to five groups （n = 5） according to developmental stages： embryonic （embryonic 15 days）, neonatal （postnatal 5 days）, juvenile （postnatal 1 month）, adult （postnatal 3 months）, and senile （postnatal 18 months）. MAIN OUTCOME MEASURES： Detection of mRNA expression of Rho-A, Rac-1, CRMP-1, and Tub β3 during various hippocampal developmental stages by reverse-transcription polymerase chain reaction. RESULTS： Hippocampal mRNA expression of Rho-A, as well as Rac-1, reached peak levels at embryonic, juvenile, and senile stages, and was relatively less during neonatal and adult stages. mRNA expression of Rac-1 was greater than Rho-A during each hippocampal developmental stage. CRMP-1 mRNA expression levels were as follows： embryonic 〉 neonatal 〉 juvenile 〉 adult 〈 senile, while Tubβ3 mRNA expression was embryonic 〉 neonatal 〉 juvenile 〉 adult = senile. CONCLUSION： Rho-A and Rac-1 shared similar expression profiles, which demonstrated similar variations during the entire rat hippocampus developmental process. However, Rac-1 mRNA expression remained greater than Rho-A. Both CRMP-1 and Tubβ3 mRNA expression profiles gradually declined during hippocampal development from embryonic to adult stages. Tubβ3 mRNA expression arrested during the adult stage, and CRMP-1 mRNA expression increased during the senile stage.
