The Multifaceted Roles of KCC2 in Cortical Development.

Mari A Virtanen, Pavel Uvarov, Martina Mavrovic, Jean Christophe Poncer, Kai Kaila

Journal: Trends in neurosciences 2021;44(5):378-392

PMID: 33640193

Free Full Text on Elsevier Science View on PubMed

Abstract

KCC2, best known as the neuron-specific chloride-extruder that sets the strength and polarity of GABAergic currents during neuronal maturation, is a multifunctional molecule that can regulate cytoskeletal dynamics via its C-terminal domain (CTD). We describe the molecular and cellular mechanisms involved in the multiple functions of KCC2 and its splice variants, ranging from developmental apoptosis and the control of early network events to the formation and plasticity of cortical dendritic spines. The versatility of KCC2 actions at the cellular and subcellular levels is also evident in mature neurons during plasticity, disease, and aging. Thus, KCC2 has emerged as one of the most important molecules that shape the overall neuronal phenotype.

Address: Molecular and Integrative Biosciences, University of Helsinki, 00014 Helsinki, Finland; Neuroscience Center, Helsinki Institute of Life Science, University of Helsinki, 00014 Helsinki, Finland.; Molecular and Integrative Biosciences, University of Helsinki, 00014 Helsinki, Finland; Neuroscience Center, Helsinki Institute of Life Science, University of Helsinki, 00014 Helsinki, Finland; Department of Molecular Medicine, University of Oslo, 0372 Oslo, Norway.; INSERM, UMRS 1270, 75005 Paris, France; Sorbonne Université, 75005 Paris, France; Institut du Fer à Moulin, 75005 Paris, France.; Molecular and Integrative Biosciences, University of Helsinki, 00014 Helsinki, Finland; Neuroscience Center, Helsinki Institute of Life Science, University of Helsinki, 00014 Helsinki, Finland. Electronic address: [email protected].

DOI: 10.1016/j.tins.2021.01.004

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MeSH Terms: Chlorides, Humans, Neurons, Symporters