Mical （molecule interacting with CasL） represent a conserved family of cytosolic multidomain proteins that has been shown to be as- sociated with a variety of cellular processes, including axon guidance, cell moveme...Mical （molecule interacting with CasL） represent a conserved family of cytosolic multidomain proteins that has been shown to be as- sociated with a variety of cellular processes, including axon guidance, cell movement, cell-cell junction formation, vesicle trafficking and cancer cell metastasis. However, the expression and function of these genes during embryonic development have not been comprehen- sively characterized, especially in vertebrate species, although some limited in vivo studies have been carried out in neural and muscula- ture systems of Drosophila and in neural systems of vertebrates. So far, no mical family homologs have been reported in zebrafish, an ideal vertebrate model for the study of developmental processes. Here we report eight homologs of mical family genes in zebrafish and their expression profiles during embryonic development. Consistent with the findings in Drosophila and mammals, most zebra_fish mical family genes display expression in neural and musculature systems. In addition, five mical homologs are detected in heart, and one, mi- call2a, in blood vessels. Our data established an important basis for further functional studies of mical family genes in zebrafish, and suggest a possible role for mical genes in cardiovascular development.展开更多
The internalization of essential nutrients,lipids and receptors is a crucial process for all eukaryotic cells.Accordingly,endocytosis is highly conserved across cell types and species.Once internalized,small cargocont...The internalization of essential nutrients,lipids and receptors is a crucial process for all eukaryotic cells.Accordingly,endocytosis is highly conserved across cell types and species.Once internalized,small cargocontaining vesicles fuse with early endosomes(also known as sorting endosomes),where they undergo segregation to distinct membrane regions and are sorted and transported on through the endocytic pathway.Although the mechanisms that regulate this sorting are still poorly understood,some receptors are directed to late endosomes and lysosomes for degradation,whereas other receptors are recycled back to the plasma membrane;either directly or through recycling endosomes.The Rab family of small GTP-binding proteins plays crucial roles in regulating these trafficking pathways.Rabs cycle from inactive GDP-bound cytoplasmic proteins to active GTP-bound membraneassociated proteins,as a consequence of the activity of multiple specific GTPase-activating proteins(GAPs) and GTP exchange factors(GEFs).Once bound to GTP,Rabs interact with a multitude of effector proteins that carry out Rab-specific functions.Recent studies have shown that some of these effectors are also interaction partners for the C-terminal Eps15 homology(EHD) proteins,which are also intimately involved in endocytic regulation.A particularly interesting example of common Rab-EHD interaction partners is the MICALlike protein,MICAL-L1.MICAL-L1 and its homolog,MICAL-L2,belong to the larger MICAL family of proteins,and both have been directly implicated in regulating endocytic recycling of cell surface receptors and junctional proteins,as well as controlling cytoskeletal rearrangement and neurite outgrowth.In this review,we summarize the functional roles of MICAL and Rab proteins,and focus on the significance of their interactions and the implications for endocytic transport.展开更多
Objective To investigate the clinical and genetic variation characteristics of a child with autosomal dominant lateral temporal lobe epilepsy caused by de novo variation of the MICALl gene.Methods Clinical data of the...Objective To investigate the clinical and genetic variation characteristics of a child with autosomal dominant lateral temporal lobe epilepsy caused by de novo variation of the MICALl gene.Methods Clinical data of the patient with autosomal dominant lateral temporal lobe epilepsy caused by MICALl gene variation diagnosed in Children's Hospital of Soochow University in August 2019 were collected.The whole exome sequencing was performed on the core members of the family,and the characteristics of gene variations were analyzed.Results The proband,a 10 years and 5 months old boy,was admitted to the hospital because of"intermittent convulsions for 7 years".The clinical manifestations included focal or generalized tonic-clonic seizures and hearing aura,with normal language and intellectual development.No abnormalities were found in the T,and fluid attenuated inversion recovery sequences of the cranial 3.0 T magnetic resonance imaging and 3D thinslice magnetic resonance imaging.Long-range video electroencephalogram showed the distribution of spinous and slow spinous waves in the left frontal and temporal areas.The results of whole exome gene sequencing in the core family members showed heterozygous de novo missense variation in the MICALI gene of the proband(NM_022765):c.763G>T(exon6)(p.Val255Leu)that had not been reported.According to American College of Medical Geneticsand Genomicssand Association for Molecular Pathology guidelines(2015),the mutation was considered potentially pathogenic.The application of antiepilepticdrugsswaseffectivein controllingepilepticcseizures.ConclusionAuditory symptoms are main clinical manifestations for the child with autosomal dominant lateral temporal lobe epilepsy.Antiepileptic drugs can effectively control epileptic seizures of the child,and the MICALl gene c.763G>T(p.Val255Leu)mutation is the genetic cause of the proband.展开更多
基金supported by National Natural Science Foundation of China (Nos. 30721064 and 30730056, 30620120101)National Basic Research Program of China (973 Program) (Nos. 2005CB522504, 2006CB943801 and 2007CB914502)
文摘Mical （molecule interacting with CasL） represent a conserved family of cytosolic multidomain proteins that has been shown to be as- sociated with a variety of cellular processes, including axon guidance, cell movement, cell-cell junction formation, vesicle trafficking and cancer cell metastasis. However, the expression and function of these genes during embryonic development have not been comprehen- sively characterized, especially in vertebrate species, although some limited in vivo studies have been carried out in neural and muscula- ture systems of Drosophila and in neural systems of vertebrates. So far, no mical family homologs have been reported in zebrafish, an ideal vertebrate model for the study of developmental processes. Here we report eight homologs of mical family genes in zebrafish and their expression profiles during embryonic development. Consistent with the findings in Drosophila and mammals, most zebra_fish mical family genes display expression in neural and musculature systems. In addition, five mical homologs are detected in heart, and one, mi- call2a, in blood vessels. Our data established an important basis for further functional studies of mical family genes in zebrafish, and suggest a possible role for mical genes in cardiovascular development.
基金Supported by The National Institutes of Health grants R01GM074876 (Caplan S and Naslavsky N),R01GM087455 (Caplan S),the Nebraska Dept. of Health (Naslavsky N)P20 RR018759 from the National Center
文摘The internalization of essential nutrients,lipids and receptors is a crucial process for all eukaryotic cells.Accordingly,endocytosis is highly conserved across cell types and species.Once internalized,small cargocontaining vesicles fuse with early endosomes(also known as sorting endosomes),where they undergo segregation to distinct membrane regions and are sorted and transported on through the endocytic pathway.Although the mechanisms that regulate this sorting are still poorly understood,some receptors are directed to late endosomes and lysosomes for degradation,whereas other receptors are recycled back to the plasma membrane;either directly or through recycling endosomes.The Rab family of small GTP-binding proteins plays crucial roles in regulating these trafficking pathways.Rabs cycle from inactive GDP-bound cytoplasmic proteins to active GTP-bound membraneassociated proteins,as a consequence of the activity of multiple specific GTPase-activating proteins(GAPs) and GTP exchange factors(GEFs).Once bound to GTP,Rabs interact with a multitude of effector proteins that carry out Rab-specific functions.Recent studies have shown that some of these effectors are also interaction partners for the C-terminal Eps15 homology(EHD) proteins,which are also intimately involved in endocytic regulation.A particularly interesting example of common Rab-EHD interaction partners is the MICALlike protein,MICAL-L1.MICAL-L1 and its homolog,MICAL-L2,belong to the larger MICAL family of proteins,and both have been directly implicated in regulating endocytic recycling of cell surface receptors and junctional proteins,as well as controlling cytoskeletal rearrangement and neurite outgrowth.In this review,we summarize the functional roles of MICAL and Rab proteins,and focus on the significance of their interactions and the implications for endocytic transport.
文摘Objective To investigate the clinical and genetic variation characteristics of a child with autosomal dominant lateral temporal lobe epilepsy caused by de novo variation of the MICALl gene.Methods Clinical data of the patient with autosomal dominant lateral temporal lobe epilepsy caused by MICALl gene variation diagnosed in Children's Hospital of Soochow University in August 2019 were collected.The whole exome sequencing was performed on the core members of the family,and the characteristics of gene variations were analyzed.Results The proband,a 10 years and 5 months old boy,was admitted to the hospital because of"intermittent convulsions for 7 years".The clinical manifestations included focal or generalized tonic-clonic seizures and hearing aura,with normal language and intellectual development.No abnormalities were found in the T,and fluid attenuated inversion recovery sequences of the cranial 3.0 T magnetic resonance imaging and 3D thinslice magnetic resonance imaging.Long-range video electroencephalogram showed the distribution of spinous and slow spinous waves in the left frontal and temporal areas.The results of whole exome gene sequencing in the core family members showed heterozygous de novo missense variation in the MICALI gene of the proband(NM_022765):c.763G>T(exon6)(p.Val255Leu)that had not been reported.According to American College of Medical Geneticsand Genomicssand Association for Molecular Pathology guidelines(2015),the mutation was considered potentially pathogenic.The application of antiepilepticdrugsswaseffectivein controllingepilepticcseizures.ConclusionAuditory symptoms are main clinical manifestations for the child with autosomal dominant lateral temporal lobe epilepsy.Antiepileptic drugs can effectively control epileptic seizures of the child,and the MICALl gene c.763G>T(p.Val255Leu)mutation is the genetic cause of the proband.
