A role for KCC3 in maintaining cell volume of peripheral nerve fibers. (February 2019)

• Record Type: Journal Article
• Authors: Flores, Bianca; Schornak, Cara C.; Delpire, Eric
• Is Part Of: Neurochemistry international. Volume 123(2019)
• Page Start: 114
• Page End: 124
• Publication Date: 2019-02
• Subjects: KCC3 -- HMSN/ACC -- ACCPN -- Andermann syndrome -- T991A -- Peripheral neuropathy; Neurochemistry -- Periodicals; Neurochemistry -- Periodicals; Neurochimie -- Périodiques; Neurochemistry; Periodicals; 612.804205
• DOI: 10.1016/j.neuint.2018.01.009
• Languages: English
• ISSNs: 0197-0186

Abstract

Abstract: The potassium chloride cotransporter, KCC3, is an electroneutral cotransporter expressed in the peripheral and central nervous system. KCC3 is responsible for the efflux of K + and Cl − in neurons to help maintain cell volume and intracellular chloride levels. A loss-of-function (LOF) of KCC3 causes Hereditary Motor Sensory Neuropathy with Agenesis of the Corpus Callosum (HMSN/ACC) in a population of individuals in the Charlevoix/Lac-Saint-Jean region of Quebec, Canada. A variety of mouse models have been created to understand the physiological and deleterious effects of a KCC3 LOF. Though this KCC3 LOF in mouse models has recapitulated the peripheral neuropathy phenotype of HMSN/ACC, we still know little about the development of the disease pathophysiology. Interestingly, the most recent KCC3 mouse model that we created recapitulated a peripheral neuropathy-like phenotype originating from a KCC3 gain-of-function (GOF). Despite the past two decades of research in attempting to understand the role of KCC3 in disease, we still do not understand how dysfunction of this cotransporter can lead to the pathophysiology of peripheral neuropathy. This review focuses on the function of KCC3 in neurons and its role in human and health and disease. Highlights: Disruption in KCC3 leads to a hereditary sensory motor neuropathy disorder. Both loss and gain of KCC3 function lead to locomotor deficits. KCC3 is a protein that functions to maintain and regulate cell volume. KCC3 LOF results in nerve fiber swelling whereas KCC3 GOF results in their shrinkage. Loss of KCC3 in sensory proprioceptive neurons leads to a locomotor phenotype.