Molecular cloning and biochemical characterization of a truncated, secreted member of the human family of Ca2+-activated Cl- channels'

A novel family of chloride channel proteins has recently been discovered in cluding two bovine (Lu-ECAM-1, bCLCA1), one murine (mCLCA1), and two human (hCLCA1 and hCLCA2) members. Here, we describe the cloning, expression, and molecular characterization of a truncated human homolog, tentatively named hCLCA3. It was cloned from a human spleen cDNA library and is expressed in numerous tissues including lung, trachea, spleen, thymus, and mammary glan d as determined by reverse transcriptase-polymerase chain reaction. Unlike all previously known CLCA family members which consistently encode an appro ximately 125-kDa transmembrane protein that is cleaved to form a heterodime r of two proteins of approximately 90 and 35 kDa, the 3.6-kb hCLCA3 mRNA en codes a 37-kDa glycoprotein that corresponds to the N-terminal extracellula r domain of its homologs. Moreover, when expressed in human embryonic kidne y 293 or Chinese hamster ovary cells, this 37-kDa glycoprotein is secreted into the culture supernatant. These observations suggest that hCLCA3 is a s tructurally divergent member of the CLCA family of proteins and that it doe s not act as a channel protein but has distinct, yet unidentified functions . (C) 1999 Published by Elsevier Science B.V. All rights reserved.