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Plasma membrane localization of MLC1 regulates cellular morphology and motility

Title
Plasma membrane localization of MLC1 regulates cellular morphology and motility
Authors
Hwang, JunmoVu, Minh HungKim, Min-SikIm, Hyun Ho
DGIST Authors
Kim, Min-Sik
Issue Date
2019-12
Citation
Molecular Brain, 12(1), 116
Type
Article
Article Type
Article
Author Keywords
MLC1LeukodystrophyActin remodelingFilopodiaLamellipodiaCell motility
Keywords
MEGALENCEPHALIC LEUKOENCEPHALOPATHYSUBCORTICAL CYSTSARP2/3 COMPLEXCATION CHANNELACTINASTROCYTESMUTATIONSMIGRATIONPROTEINWASP
ISSN
1756-6606
Abstract
Background: Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare form of infantile-onset leukodystrophy. The disorder is caused primarily by mutations of MLC1 that leads to a series of phenotypic outcomes including vacuolation of myelin and astrocytes, subcortical cysts, brain edema, and macrocephaly. Recent studies have indicated that functional interactions among MLC1, GlialCAM, and ClC-2 channels play key roles in the regulation of neuronal, glial and vascular homeostasis. However, the physiological role of MLC1 in cellular homeostatic communication remains poorly understood. In the present study, we investigated the cellular function of MLC1 and its effects on cell-cell interactions. Methods: MLC1-dependent cellular morphology and motility were analyzed by using confocal and live cell imaging technique. Biochemical approaches such as immunoblotting, co-immunoprecipitation, and surface biotinylation were conducted to support data. Results: We found that the altered MLC1 expression and localization led to a great alteration in cellular morphology and motility through actin remodeling. MLC1 overexpression induced filopodia formation and suppressed motility. And, MLC1 proteins expressed in patient-derived MLC1 mutants resulted in trapping in the ER although no changes in morphology or motility were observed. Interestingly knockdown of Mlc1 induced Arp3-Cortactin interaction, lamellipodia formation, and increased the membrane ruffling of the astrocytes. These data indicate that subcellular localization of expressed MLC1 at the plasma membrane is critical for changes in actin dynamics through ARP2/3 complex. Thus, our results suggest that misallocation of pathogenic mutant MLC1 may disturbs the stable cell-cell communication and the homeostatic regulation of astrocytes in patients with MLC. © 2019 The Author(s).
URI
http://hdl.handle.net/20.500.11750/11402
DOI
10.1186/s13041-019-0540-6
Publisher
BioMed Central Ltd.
Related Researcher
  • Author Kim, Min-Sik Laboratory for QBIO and Precision Medicine
  • Research Interests Cancer Proteogenomics, Biomarker Discovery, Integrative Multi-Omics
Files:
Collection:
Department of New BiologyLaboratory for QBIO and Precision Medicine1. Journal Articles


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