GPM6A Membrane Protein Introduction

Introduction of GPM6A

Neuronal membrane glycoprotein M6-a (GPM6A), also known as M6a, M6A, is a protein that in humans is encoded by the GPM6A gene. GPM6A is a membrane glycoprotein that is abundantly expressed in CNS neurons, especially in the hippocampus. The functions of GPM6A in CNS include regulation of filopodium formation, neurite outgrowth and, most likely, synaptogenesis. Overexpression of GPM6A in rat hippocampal neurons as well as in neuronal (N2a, PC12) and non-neuronal cell lines (COS7) induces extensive formation of filopodia. Inhibition of endogenous GPM6A expression by siRNA reduces the number of filopodia and synaptic clusters. The filopodia induced by GPM6A are highly motile and become stabilized upon contact with presynaptic regions. Mutational analysis identified cysteine residues in the large extracellular domain of Gpm6a to be critical for the process of GPM6A induced filopodium formation. In addition, the localization of GPM6A in the membrane lipid microdomains and the activity of Src kinases and MAPK are required for this process.

Basic Information of GPM6A
Protein Name	Neuronal membrane glycoprotein M6-a
Gene Name	GPM6A
Aliases	M6a, M6A
Organism	Homo sapiens (Human)
UniProt ID	P51674
Transmembrane Times	4
Length (aa)	278
Sequence	MEENMEEGQTQKGCFECCIKCLGGIPYASLIATILLYAGVALFCGCGHEALSGTVNILQTYFEMARTAGDTLDVFTMIDIFKYVIYGIAAAFFVYGILLMVEGFFTTGAIKDLYGDFKITTCGRCVSAWFIMLTYLFMLAWLGVTAFTSLPVYMYFNLWTICRNTTLVEGANLCLDLRQFGIVTIGEEKKICTVSENFLRMCESTELNMTFHLFIVALAGAGAAVIAMVHYLMVLSANWAYVKDACRMQKYEDIKSKEEQELHDIHSTRSKERLNAYT

Function of GPM6A Membrane Protein

GPM6A was originally identified as a stress- and antidepressant-responsive gene in the hippocampus in a number of animal models of chronic stress. Altered hippocampal expression of GPM6A has been reported in postmortem brain of depressed suicides of humans. Moreover, polymorphisms in the GPM6A gene sequence are associated with pathological conditions such as bipolar disorders, schizophrenia, and claustrophobia. In addition, an increased level of GPM6A resulting from de novo duplication of the GPM6A gene has been reported in a patient with a learning disability and behavioral anomalies.

Four transmembrane domains, putative sites of glycosylation, palmitoylation, and phosphorylation. Fig.1 The structural domains of GPM6a. (Ito, 2018)

Application of GPM6A Membrane Protein in Literature

Gu X., et al. miR-124 and miR-9 mediated downregulation of HDAC5 promotes neurite development through activating MEF2C-GPM6A pathway. J Cell Physiol. 2018, 233(1): 673-687. PubMed ID: 28332716

This article reveals that HDAC5 appears as a cellular conductor of MEF2C and GPM6A activity. It is regulated by miR-124 and miR-9 to control the development of neurite.
Shi H.B., et al. Construction of Gpm6a/Reelin^GFPCreERT2 by BAC recombination using a specific gene in hepatic mesothelial or stellate cells. World J Gastroenterol. 2017, 23(2): 224-231. PubMed ID: 28127196

Authors in this group successfully prepared the construct of Gpm6a^GFPCreERT2 or Reelin^GFPCreERT2, which laid the foundation for tracing the hepatic stellate cell lineage and studying its function.
Alvarez Juliá A., et al. Neuronal filopodium formation induced by the membrane glycoprotein M6a (Gpm6a) is facilitated by coronin-1a, Rac1, and p21-activated kinase 1 (Pak1). J Neurochem. 2016, 137(1): 46-61. PubMed ID: 26809475

The article provides a mechanistic insight into the process of Gpm6a-induced neuronal filopodium formation. Neuronal filopodium formation induced by Gpm6a is facilitated by coronin-1a, Rac1, and p21-activated kinase 1.
Charfi C., et al. Identification of GPM6A and GPM6B as potential new human lymphoid leukemia-associated oncogenes. Cell Oncol (Dordr). 2014, 37(3): 179-91. PubMed ID: 24916915

The article reveals that GPM6A and GPM6B may act as novel oncogenes in the development of human lymphoid leukemia-associated oncogenes.
Gregor A., et al. Altered GPM6A/M6 dosage impairs cognition and causes phenotypes responsive to cholesterol in human and Drosophila. Hum Mutat. 2014, 35(12): 1495-505. PubMed ID: 25224183

This article reports that correct GPM6A/M6 levels are essential for cognitive function while altered GPM6A/M6 dosage impairs cognition and lead to phenotypes responsive to cholesterol in human and Drosophila.

GPM6A Preparation Options

To obtain the soluble and functional target protein, the versatile Magic™ membrane protein production platform in Creative Biolabs enables many flexible options, from which you can always find a better match for your particular project. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-GPM6A antibody development services.

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Reference

Ito Y, et al. (2018). Glycoprotein M6a as a signaling transducer in neuronal lipid rafts. Neurosci Res. 128: 19-24.

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