Claudin-11, a hypomyelinating leukodystrophy 22 (HLD22)-responsible protein, uniquely interacts with shroom-2 to change cell phenotypes
Oligodendroglial cells are a type of glial cell in the central nervous system (CNS) that wrap neuronal axons with differentiated plasma membranes known as myelin sheaths. While the physiological functions of oligodendrocytes, such as generating saltatory conduction and protecting neuronal axons, are...
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Elsevier
2025-01-01
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| Series: | BBA Advances |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667160325000225 |
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| author | Sakurako Kobayashi Takanori Yokoi Takeru Omata Hideji Yako Yuki Miyamoto Junji Yamauchi |
| author_facet | Sakurako Kobayashi Takanori Yokoi Takeru Omata Hideji Yako Yuki Miyamoto Junji Yamauchi |
| author_sort | Sakurako Kobayashi |
| collection | DOAJ |
| description | Oligodendroglial cells are a type of glial cell in the central nervous system (CNS) that wrap neuronal axons with differentiated plasma membranes known as myelin sheaths. While the physiological functions of oligodendrocytes, such as generating saltatory conduction and protecting neuronal axons, are well understood, the physiological and/or pathophysiological molecular mechanisms governing their differentiation before myelination remain unclear. In this study, we describe for the first time that claudin-11, a protein associated with hypomyelinating leukodystrophy 22 (HLD22), interacts with shroom-2, a presumable adaptor protein containing the PSD95, DLG1, and ZO-1 (PDZ) domain. Knockdown of claudin-11 using specific siRNA resulted in a decrease in morphological changes and marker proteins in the FBD-102b oligodendroglial model undergoing differentiation. Transfection of the C-terminal PDZ ligand sequence of claudin-11, which was found to interact with the PDZ domain of shroom-2, also reduced these phenotypic changes. The HLD22-associated mutated sequence in claudin-11 failed to interact with the PDZ domain of shroom-2. Furthermore, knockdown of shroom-2 or transfection of the PDZ domain of shroom-2, which is involved in the interaction with claudin-11, resulted in decreased morphological changes and marker protein expression. These changes were linked to the phosphorylation states of Akt kinase, a key signaling molecule in oligodendroglial cell differentiation and myelination. These results suggest that the interaction between claudin-11 and shroom-2 plays a key role in shaping cell morphology, providing insights into the molecular mechanisms underlying oligodendroglial differentiation before myelination, as well as potential pathological mechanisms associated with HLD22 at the molecular and cellular levels. |
| format | Article |
| id | doaj-art-48dd3628a7114839a3d85fa8b54783ff |
| institution | OA Journals |
| issn | 2667-1603 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | BBA Advances |
| spelling | doaj-art-48dd3628a7114839a3d85fa8b54783ff2025-08-20T02:10:03ZengElsevierBBA Advances2667-16032025-01-01710015910.1016/j.bbadva.2025.100159Claudin-11, a hypomyelinating leukodystrophy 22 (HLD22)-responsible protein, uniquely interacts with shroom-2 to change cell phenotypesSakurako Kobayashi0Takanori Yokoi1Takeru Omata2Hideji Yako3Yuki Miyamoto4Junji Yamauchi5Laboratory of Molecular Neuroscience and Neurology, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, JapanLaboratory of Molecular Neuroscience and Neurology, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, JapanLaboratory of Molecular Neuroscience and Neurology, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, JapanLaboratory of Molecular Neuroscience and Neurology, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, JapanLaboratory of Molecular Neuroscience and Neurology, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, Japan; Laboratory of Molecular Pharmacology, National Research Institute for Child Health and Development, Tokyo 157-8535, JapanLaboratory of Molecular Neuroscience and Neurology, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, Japan; Laboratory of Molecular Pharmacology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan; Corresponding author at: Laboratory of Molecular Neuroscience and Neurology, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan,Oligodendroglial cells are a type of glial cell in the central nervous system (CNS) that wrap neuronal axons with differentiated plasma membranes known as myelin sheaths. While the physiological functions of oligodendrocytes, such as generating saltatory conduction and protecting neuronal axons, are well understood, the physiological and/or pathophysiological molecular mechanisms governing their differentiation before myelination remain unclear. In this study, we describe for the first time that claudin-11, a protein associated with hypomyelinating leukodystrophy 22 (HLD22), interacts with shroom-2, a presumable adaptor protein containing the PSD95, DLG1, and ZO-1 (PDZ) domain. Knockdown of claudin-11 using specific siRNA resulted in a decrease in morphological changes and marker proteins in the FBD-102b oligodendroglial model undergoing differentiation. Transfection of the C-terminal PDZ ligand sequence of claudin-11, which was found to interact with the PDZ domain of shroom-2, also reduced these phenotypic changes. The HLD22-associated mutated sequence in claudin-11 failed to interact with the PDZ domain of shroom-2. Furthermore, knockdown of shroom-2 or transfection of the PDZ domain of shroom-2, which is involved in the interaction with claudin-11, resulted in decreased morphological changes and marker protein expression. These changes were linked to the phosphorylation states of Akt kinase, a key signaling molecule in oligodendroglial cell differentiation and myelination. These results suggest that the interaction between claudin-11 and shroom-2 plays a key role in shaping cell morphology, providing insights into the molecular mechanisms underlying oligodendroglial differentiation before myelination, as well as potential pathological mechanisms associated with HLD22 at the molecular and cellular levels.http://www.sciencedirect.com/science/article/pii/S2667160325000225Claudin-11Shroom-2HLD22OligodendrocyteDifferentiation before myelination |
| spellingShingle | Sakurako Kobayashi Takanori Yokoi Takeru Omata Hideji Yako Yuki Miyamoto Junji Yamauchi Claudin-11, a hypomyelinating leukodystrophy 22 (HLD22)-responsible protein, uniquely interacts with shroom-2 to change cell phenotypes BBA Advances Claudin-11 Shroom-2 HLD22 Oligodendrocyte Differentiation before myelination |
| title | Claudin-11, a hypomyelinating leukodystrophy 22 (HLD22)-responsible protein, uniquely interacts with shroom-2 to change cell phenotypes |
| title_full | Claudin-11, a hypomyelinating leukodystrophy 22 (HLD22)-responsible protein, uniquely interacts with shroom-2 to change cell phenotypes |
| title_fullStr | Claudin-11, a hypomyelinating leukodystrophy 22 (HLD22)-responsible protein, uniquely interacts with shroom-2 to change cell phenotypes |
| title_full_unstemmed | Claudin-11, a hypomyelinating leukodystrophy 22 (HLD22)-responsible protein, uniquely interacts with shroom-2 to change cell phenotypes |
| title_short | Claudin-11, a hypomyelinating leukodystrophy 22 (HLD22)-responsible protein, uniquely interacts with shroom-2 to change cell phenotypes |
| title_sort | claudin 11 a hypomyelinating leukodystrophy 22 hld22 responsible protein uniquely interacts with shroom 2 to change cell phenotypes |
| topic | Claudin-11 Shroom-2 HLD22 Oligodendrocyte Differentiation before myelination |
| url | http://www.sciencedirect.com/science/article/pii/S2667160325000225 |
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