Myosin heavy chain 9(MYH9),a non-muscle myosin heavy chain protein,has been identified as a significant factor in gastrointestinal(GI)oncology,with its overexpression in various GI malignancies such as esophageal,gast...Myosin heavy chain 9(MYH9),a non-muscle myosin heavy chain protein,has been identified as a significant factor in gastrointestinal(GI)oncology,with its overexpression in various GI malignancies such as esophageal,gastric,and co-lorectal cancers being associated with poor prognosis and playing a role in tumor invasion and metastasis.This comprehensive review synthesizes the current body of knowledge regarding MYH9’s role in GI tumors,focusing on its molecular mechanisms,including its interaction with key signaling pathways like the phosphatidylinositol 3-kinase/protein kinase B/mechanistic target of rapamycin axis,which suggests a role in cancer cell survival,proliferation,and epithelial-mesenchymal transition.The review also explores MYH9’s potential as a therapeutic target,with preclinical models demonstrating promising results in inhibiting tumor growth and enhancing chemosensitivity.The evidence suggests that MYH9 is a multifaceted protein with significant implications in GI tumor biology,warranting further research to elucidate its mechanisms of action and develop targeted therapies that could improve patient outcomes.展开更多
N-methyl-D-aspartate receptor(NMDAR)trafficking is a key process in the regulation of synaptic efficacy and brain function.However,the molecular mechanism underlying the surface transport of NMDARs is largely unknown....N-methyl-D-aspartate receptor(NMDAR)trafficking is a key process in the regulation of synaptic efficacy and brain function.However,the molecular mechanism underlying the surface transport of NMDARs is largely unknown.Here we identified myosin Va(MyoVa)as the specific motor protein that traffics NMDARs in hippocampal neurons.We found that MyoVa associates with NMDARs through its cargo binding domain.This association was increased during NMDAR surface transport.Knockdown of MyoVa suppressed NMDAR transport.We further demonstrated that Ca^(2+)/calmodulin-dependent protein kinase Ⅱ(CaMKⅡ)regulates NMDAR transport through its direct interaction with MyoVa.Furthermore,MyoVa employed Rab11 family-interacting protein 3(Rab11/FIP3)as the adaptor proteins to couple themselves with NMDARs during their transport.Accordingly,the knockdown of FIP3 impairs hippocampal memory.Together,we conclude that in hippocampal neurons,MyoVa conducts active transport of NMDARs in a CaMKII-dependent manner.展开更多
AIM: To study preliminarily the properties of myosin light chain kinase (MLCK) in rabbit liver. METHODS: The expression of MLCK was detected by reverse transcription-polymerase chain reaction(RT-PCR); the MLCK was obt...AIM: To study preliminarily the properties of myosin light chain kinase (MLCK) in rabbit liver. METHODS: The expression of MLCK was detected by reverse transcription-polymerase chain reaction(RT-PCR); the MLCK was obtained from rabbit liver, and its activity was analyzed by gamma-(32)P incorporation technique to detect the phosphorylation of myosin light chain. RESULTS: MLCK was expressed in rabbit liver, and the activity of the enzyme was similar to rabbit smooth muscle MLCK, and calmodulin-dependent. When the concentration was 0.65 mg x L(-1), the activity was at the highest level. CONCLUSION: MLCK expressed in rabbit liver may catalyze the phosphorylation of myosin light chain, which may play important roles in the regulation of hepatic cell functions.展开更多
The aim of this study is to investigate the functional relationship between filamin, a known actin binding protein, and myosin and the effects of filamin on the interaction between myosin and actin. Methods.Ultra cent...The aim of this study is to investigate the functional relationship between filamin, a known actin binding protein, and myosin and the effects of filamin on the interaction between myosin and actin. Methods.Ultra centrifugation method was used to investigate the binding of filamin to both phosphorylated and unphosphorylated myosins. Mg ATPase activities of both phosphorylated and unphosphorylated myosins in the presence and absence of actin were measured to observe the effects resulted from filamin actin and filamin myosin interactions. Results. It was found that filamin is also a myosin binding protein. Filamin inhibited the actin activated Mg ATPase activity of phosphorylated myosin and stimulated Mg ATPase of phosphorylated myosin in the absence of actin; in addition, filamin stimulated Mg ATPase activity of unphosphorylated myosin in both the presence or absence of actin. Conclusion. The results suggest that the effects of filamin on the myosin Mg ATPase activities are bi directional, i.e., stimulatory via binding to myosin and inhibitory via binding to actin.展开更多
Myosin XVIIIA, or MYO18A, is a unique PDZ domain-containing unconventional myosin and is evolutionarily conserved from Drosophila to vertebrates. Although there is evidence indicating its expression in the somites, wh...Myosin XVIIIA, or MYO18A, is a unique PDZ domain-containing unconventional myosin and is evolutionarily conserved from Drosophila to vertebrates. Although there is evidence indicating its expression in the somites, whether it regulates muscle function re- mains unclear. We show that the two zebrafish myo18a genes （myo18aa and myo18ab） are predominantly expressed at somite borders during early developmental stages. Knockdown of these genes or overexpression of the MYO18A PDZ domain disrupts myofiber integrity, induces myofiber lesions, and compromises the localization of dystrophin, ^-dystroglycan （^-DG） and laminin at the myotome boundaries. Cell transplantation experiments indicate that myo18a morphant myoblasts fail to form elongated myofibers in the myotomes of wild-type embryos, which can be rescued by the full-length MYO18A protein. These results suggest that MYO18A likely functions in the adhesion process that maintains the stable attachment of myofibers to ECM （extracellular matrix） and muscle integrity during early development.展开更多
Objective: To reveal the special feature of calponin (CaP) on myosins of different states. Methods: Myosin phosphorylation determination, myosin Mg^(2+)-ATPase measurement and protein binding assay were used in this s...Objective: To reveal the special feature of calponin (CaP) on myosins of different states. Methods: Myosin phosphorylation determination, myosin Mg^(2+)-ATPase measurement and protein binding assay were used in this study. The lowest CaP/myosin ratio used in the assay was 1/10000(mol/mol), which was 10 thousands-fold lower than the CaP/myosin ratio used in previous studies. Results: In the absence of actin, micro-amount of calponin (MAC) stimulated the Mg^(2+)-ATPase activities of myosin in different states slightly but significantly; and more importantly, MAC significantly increased the precipitations of unphosphorylated myosin, Ca^(2+)-dependently and independently phosphorylated myosins by MLCK but not the myosin phosphorylated by PKA. Conclusion: MAC has a high efficient and selective effect on myosin in the absence of actin.展开更多
The molecular structure of a higher plant myosin with two 174 kD heavy chains purified from the tendrils of Luffa cylindrica (L.) Roem. was viewed by electron microscopy. The myosin exhibited actin_activated MgATP...The molecular structure of a higher plant myosin with two 174 kD heavy chains purified from the tendrils of Luffa cylindrica (L.) Roem. was viewed by electron microscopy. The myosin exhibited actin_activated MgATPase activity and could be recognized immunologically by a monoclonal antibody against the skeletal muscle myosin. Electron micrographs of rotary shadowed images of this protein revealed that it had two heads with size and shape similar to those of the skeletal muscle myosin and a relatively short tail in comparison with the conventional myosin. Luffa tendril actin filaments were also visualized and occasionally other Luffa myosin_like proteins with globular structure at the tail ends were also observed. The structural similarity and immunological cross reactivity with antibodies against muscle myosin demonstrate that the 174 kD Luffa tendril myosin is a double_headed myosin. The possible involvement of myosin_actin interactions in Luffa tendril contact coiling will be the subject of further research.展开更多
Myofibrillogenesis, the process of sarcomere formation, requires close interactions of sarcomeric proteins and various components of sarcomere structures. The myosin thick filaments and M-lines are two key components ...Myofibrillogenesis, the process of sarcomere formation, requires close interactions of sarcomeric proteins and various components of sarcomere structures. The myosin thick filaments and M-lines are two key components of the sarcomere. It has been suggested that myomesin proteins of M-lines interact with myosin and titin proteins and keep the thick and titin filaments in order. However, the function of myomesin in myofibrillogenesis and sarcomere organization remained largely enigmatic. No knockout or knockdown animal models have been reported to elucidate the role of myomesin in sarcomere organization in vivo. In this study, by using the gene-specific knockdown approach in zebrafish embryos, we carded out a loss-of-function analysis of myomesin-3 and slow myosin heavy chain 1 （smyhcl） expressed specifically in slow muscles. We demonstrated that knockdown of smyhcl abolished the sarcomeric localization of myomesin-3 in slow muscles. In contrast, loss of myomesin-3 had no effect on the sarcomeric organization of thick and thin filaments as well as M- and Z-line structures. Together, these studies indicate that myosin thick filaments are required for M-line organization and M-line localization of myomesin-3. In contrast, myomesin-3 is dispensable for sarcomere organization in slow muscles.展开更多
文摘Myosin heavy chain 9(MYH9),a non-muscle myosin heavy chain protein,has been identified as a significant factor in gastrointestinal(GI)oncology,with its overexpression in various GI malignancies such as esophageal,gastric,and co-lorectal cancers being associated with poor prognosis and playing a role in tumor invasion and metastasis.This comprehensive review synthesizes the current body of knowledge regarding MYH9’s role in GI tumors,focusing on its molecular mechanisms,including its interaction with key signaling pathways like the phosphatidylinositol 3-kinase/protein kinase B/mechanistic target of rapamycin axis,which suggests a role in cancer cell survival,proliferation,and epithelial-mesenchymal transition.The review also explores MYH9’s potential as a therapeutic target,with preclinical models demonstrating promising results in inhibiting tumor growth and enhancing chemosensitivity.The evidence suggests that MYH9 is a multifaceted protein with significant implications in GI tumor biology,warranting further research to elucidate its mechanisms of action and develop targeted therapies that could improve patient outcomes.
基金supported by grants from the STI2030-Major Projects(2021ZD0203502)the National Natural Science Foundation of China(31730107,31970959,and 31671056).
文摘N-methyl-D-aspartate receptor(NMDAR)trafficking is a key process in the regulation of synaptic efficacy and brain function.However,the molecular mechanism underlying the surface transport of NMDARs is largely unknown.Here we identified myosin Va(MyoVa)as the specific motor protein that traffics NMDARs in hippocampal neurons.We found that MyoVa associates with NMDARs through its cargo binding domain.This association was increased during NMDAR surface transport.Knockdown of MyoVa suppressed NMDAR transport.We further demonstrated that Ca^(2+)/calmodulin-dependent protein kinase Ⅱ(CaMKⅡ)regulates NMDAR transport through its direct interaction with MyoVa.Furthermore,MyoVa employed Rab11 family-interacting protein 3(Rab11/FIP3)as the adaptor proteins to couple themselves with NMDARs during their transport.Accordingly,the knockdown of FIP3 impairs hippocampal memory.Together,we conclude that in hippocampal neurons,MyoVa conducts active transport of NMDARs in a CaMKII-dependent manner.
基金Supported by the National Natural Science Foundation of China(39870324,YW)Key Innovation Project of Chinese Academy of Science,P.R.China(KSCX 2-2-01,XB Yao)Grant for Excellent Young Teachers of Ministry of Education of China(99044312,YW)
文摘AIM: To study preliminarily the properties of myosin light chain kinase (MLCK) in rabbit liver. METHODS: The expression of MLCK was detected by reverse transcription-polymerase chain reaction(RT-PCR); the MLCK was obtained from rabbit liver, and its activity was analyzed by gamma-(32)P incorporation technique to detect the phosphorylation of myosin light chain. RESULTS: MLCK was expressed in rabbit liver, and the activity of the enzyme was similar to rabbit smooth muscle MLCK, and calmodulin-dependent. When the concentration was 0.65 mg x L(-1), the activity was at the highest level. CONCLUSION: MLCK expressed in rabbit liver may catalyze the phosphorylation of myosin light chain, which may play important roles in the regulation of hepatic cell functions.
文摘The aim of this study is to investigate the functional relationship between filamin, a known actin binding protein, and myosin and the effects of filamin on the interaction between myosin and actin. Methods.Ultra centrifugation method was used to investigate the binding of filamin to both phosphorylated and unphosphorylated myosins. Mg ATPase activities of both phosphorylated and unphosphorylated myosins in the presence and absence of actin were measured to observe the effects resulted from filamin actin and filamin myosin interactions. Results. It was found that filamin is also a myosin binding protein. Filamin inhibited the actin activated Mg ATPase activity of phosphorylated myosin and stimulated Mg ATPase of phosphorylated myosin in the absence of actin; in addition, filamin stimulated Mg ATPase activity of unphosphorylated myosin in both the presence or absence of actin. Conclusion. The results suggest that the effects of filamin on the myosin Mg ATPase activities are bi directional, i.e., stimulatory via binding to myosin and inhibitory via binding to actin.
基金supported by the grants from the National Science Foundation of China (No. 31271556)Association Francaise contre les Myopathies (AFM)the Agence Nationale de la Recherche (ANR-09-BLAN-0262-03) in France
文摘Myosin XVIIIA, or MYO18A, is a unique PDZ domain-containing unconventional myosin and is evolutionarily conserved from Drosophila to vertebrates. Although there is evidence indicating its expression in the somites, whether it regulates muscle function re- mains unclear. We show that the two zebrafish myo18a genes （myo18aa and myo18ab） are predominantly expressed at somite borders during early developmental stages. Knockdown of these genes or overexpression of the MYO18A PDZ domain disrupts myofiber integrity, induces myofiber lesions, and compromises the localization of dystrophin, ^-dystroglycan （^-DG） and laminin at the myotome boundaries. Cell transplantation experiments indicate that myo18a morphant myoblasts fail to form elongated myofibers in the myotomes of wild-type embryos, which can be rescued by the full-length MYO18A protein. These results suggest that MYO18A likely functions in the adhesion process that maintains the stable attachment of myofibers to ECM （extracellular matrix） and muscle integrity during early development.
文摘Objective: To reveal the special feature of calponin (CaP) on myosins of different states. Methods: Myosin phosphorylation determination, myosin Mg^(2+)-ATPase measurement and protein binding assay were used in this study. The lowest CaP/myosin ratio used in the assay was 1/10000(mol/mol), which was 10 thousands-fold lower than the CaP/myosin ratio used in previous studies. Results: In the absence of actin, micro-amount of calponin (MAC) stimulated the Mg^(2+)-ATPase activities of myosin in different states slightly but significantly; and more importantly, MAC significantly increased the precipitations of unphosphorylated myosin, Ca^(2+)-dependently and independently phosphorylated myosins by MLCK but not the myosin phosphorylated by PKA. Conclusion: MAC has a high efficient and selective effect on myosin in the absence of actin.
文摘The molecular structure of a higher plant myosin with two 174 kD heavy chains purified from the tendrils of Luffa cylindrica (L.) Roem. was viewed by electron microscopy. The myosin exhibited actin_activated MgATPase activity and could be recognized immunologically by a monoclonal antibody against the skeletal muscle myosin. Electron micrographs of rotary shadowed images of this protein revealed that it had two heads with size and shape similar to those of the skeletal muscle myosin and a relatively short tail in comparison with the conventional myosin. Luffa tendril actin filaments were also visualized and occasionally other Luffa myosin_like proteins with globular structure at the tail ends were also observed. The structural similarity and immunological cross reactivity with antibodies against muscle myosin demonstrate that the 174 kD Luffa tendril myosin is a double_headed myosin. The possible involvement of myosin_actin interactions in Luffa tendril contact coiling will be the subject of further research.
基金supported by a research grant(MB-8716-08) from United States-Israel Binational Agriculture Research and Development Fund to SJD and a NIH grant(DA14546) to SCELiangyi Xue was supported by a Pao Yu-Kong and Pao Zhao-Long Scholarship for Chinese Scholars Studying Abroad from Ningbo University,China
文摘Myofibrillogenesis, the process of sarcomere formation, requires close interactions of sarcomeric proteins and various components of sarcomere structures. The myosin thick filaments and M-lines are two key components of the sarcomere. It has been suggested that myomesin proteins of M-lines interact with myosin and titin proteins and keep the thick and titin filaments in order. However, the function of myomesin in myofibrillogenesis and sarcomere organization remained largely enigmatic. No knockout or knockdown animal models have been reported to elucidate the role of myomesin in sarcomere organization in vivo. In this study, by using the gene-specific knockdown approach in zebrafish embryos, we carded out a loss-of-function analysis of myomesin-3 and slow myosin heavy chain 1 （smyhcl） expressed specifically in slow muscles. We demonstrated that knockdown of smyhcl abolished the sarcomeric localization of myomesin-3 in slow muscles. In contrast, loss of myomesin-3 had no effect on the sarcomeric organization of thick and thin filaments as well as M- and Z-line structures. Together, these studies indicate that myosin thick filaments are required for M-line organization and M-line localization of myomesin-3. In contrast, myomesin-3 is dispensable for sarcomere organization in slow muscles.
