ArticleHuman molecular genetics2021
Identification of the GlialCAM interactome: the G protein-coupled receptors GPRC5B and GPR37L1 modulate megalencephalic leukoencephalopathy proteins.
Article in Human molecular genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 27 citations in OpenAlex.
- Review
- Written in the Stars: Astrocyte Biology From Evolution to Disease.Acta physiologica (Oxford, England) · 2026Review
- Astrocytes viewed through the lens of their proteomes and subproteomes.Nature reviews. Neuroscience · 2026Review
- Patient and Family Perspectives on Clinical Outcomes in Therapy Trials in Megalencephalic Leukoencephalopathy with Subcortical Cysts: An Open Inventory.Neuropediatrics · 2026Article
- Altered Mechanical Properties of Astrocytes Lacking MLC1: Implications for the Leukodystrophy MLC.Glia · 2026Article
- Molecular profiling of brain endothelial cell to astrocyte endfoot communication in mouse and human.Nature communications · 2025Article
- Multiple sclerosis: an immune attack on astrocyte-mediated ion and water homeostasis.Nature reviews. Neurology · 2025Review
- Gene therapy rescues brain edema and motor function in a mouse model of megalencephalic leukoencephalopathy with subcortical cysts.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Neuroglial Pathophysiology of Leukodystrophies.Advances in neurobiology · 2025Review
- Development of perivascular astrocyte processes.Frontiers in neuroscience · 2025Review
- Megalencephalic leukoencephalopathy with subcortical cysts: a variant update and review of the literature.Frontiers in genetics · 2024Article
- Aquaporin-4 and GPRC5B: old and new players in controlling brain oedema.Brain : a journal of neurology · 2023Article
- A Preliminary Comparison of the Methylome and Transcriptome from the Prefrontal Cortex Across Alzheimer's Disease and Lewy Body Dementia.Journal of Alzheimer's disease reports · 2023Article
- GPR37 Receptors and Megalencephalic Leukoencephalopathy with Subcortical Cysts.International journal of molecular sciences · 2022Review
- Mouse Mutants ofInternational journal of molecular sciences · 2022Review
- Mlc1-Expressing Perivascular Astrocytes Promote Blood-Brain Barrier Integrity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
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Authors and funding
16 authors at 7 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Megalencephalic Leukoencephalopathy with subcortical Cysts (MLC) is a type of vacuolating leukodystrophy, which is mainly caused by mutations in MLC1 or GLIALCAM. The two MLC-causing genes encode for membrane proteins of yet unknown function that have been linked to the regulation of different chloride channels such as the ClC-2 and VRAC. To gain insight into the role of MLC proteins, we have determined the brain GlialCAM interacting proteome. The proteome includes different transporters and ion channels known to be involved in the regulation of brain homeostasis, proteins related to adhesion or signaling as several G protein-coupled receptors (GPCRs), including the orphan GPRC5B and the proposed prosaposin receptor GPR37L1. Focusing on these two GPCRs, we could validate that they interact directly with MLC proteins. The inactivation of Gpr37l1 in mice upregulated MLC proteins without altering their localization. Conversely, a reduction of GPRC5B levels in primary astrocytes downregulated MLC proteins, leading to an impaired activation of ClC-2 and VRAC. The interaction between the GPCRs and MLC1 was dynamically regulated upon changes in the osmolarity or potassium concentration. We propose that GlialCAM and MLC1 associate with different integral membrane proteins modulating their functions and acting as a recruitment site for various signaling components as the GPCRs identified here. We hypothesized that the GlialCAM/MLC1 complex is working as an adhesion molecule coupled to a tetraspanin-like molecule performing regulatory effects through direct binding or influencing signal transduction events.
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