K(+)-Cl(−) cotransporter 1 (KCC1): a housekeeping membrane protein that plays key supplemental roles in hematopoietic and cancer cells

During the 1970s, a Na(+)-independent, ouabain-insensitive, N-ethylmaleimide-stimulated K(+)-Cl(−) cotransport mechanism was identified in red blood cells for the first time and in a variety of cell types afterward. During and just after the mid-1990s, three closely related isoforms were shown to account for this mechanism. They were termed K(+)-Cl(−) cotransporter 1 (KCC1), KCC3, and KCC4 according to the nomenclature of Gillen et al. (1996) who had been the first research group to uncover the molecular identity of a KCC, that is, of KCC1 in rabbit kidney. Since then, KCC1 has been found to be the most widely distributed KCC isoform and considered to act as a housekeeping membrane protein. It has perhaps received less attention than the other isoforms for this reason, but as will be discussed in the following review, there is probably more to KCC1 than meets the eye. In particular, the so-called housekeeping gene also appears to play crucial and specific roles in normal as well as pathological hematopoietic and in cancer cells.