Glycoprotein M6a as a signaling transducer in neuronal lipid rafts

Neuronal development is composed of the complex steps which involve many signaling proteins. On the other hand, there are many proteins highly expressed in the differentiated neurons at developmental stages, but of which physiological functions are not precisely known so far. Glycoprotein 6a (GPM6a) currently belongs to such proteins. This protein has four-transmembrane domains and is a member of proteolipid protein family. Recently, we demonstrated that GPM6a is highly concentrated in lipid rafts of the developing neuron with its palmitoylation, and that this molecule is involved in rapid determination of the neuronal polarity, in response to laminin, an extracellular matrix protein (Honda et al., J Neurosci 37: 4046-64 [2017]). Since lipid rafts are membrane domains enriched in sphingolipids and cholesterol, have lower fluidity than other membrane areas and are believed to be signaling "hot-spots", and here, we discuss the functions of this protein in neuronal lipid raft signaling for neuronal development.