Regulated sarcolemmal localization of the muscle-specific ClC-1 chloride channel.
The skeletal muscle-specific ClC-1 is a voltage-gated chloride channel protein. Specific antibodies against ClC-1 revealed in muscle sections a sarcolemmal staining that was absent in the myotonic arrested development of righting response (ADR) mouse muscle. The intensity of the sarcolemmal staining varied from one type of muscle to another and in lateral sections showed a typical mosaic pattern that colocalized with beta-dystroglycan and left the transverse tubule openings clear. Surprisingly, in isolated myofibers, the ClC-1 protein was absent from the sarcolemma. Instead, it localized to intracellular I band areas as soon as the myofibers were isolated. When the isolated myofibers were incubated with the kinase inhibitor staurosporine, the ClC-1 protein shifted back to the sarcolemma. Electric stimulation of the cultivated fibers had a similar effect. Also, myofibers infected with a recombinant Semliki Forest virus (SFV) expressing myc-tagged ClC-1 showed intracellular localization of the protein. The virally expressed mycClC-1 reached the Golgi apparatus but sarcolemmal staining remained nondetectable, and addition of staurosporine into the growth medium recruited the mycClC-1 to the sarcolemma. These data indicate that sarcolemmal targeting of the ClC-1 requires specific signals that are provided by the physiological environment.
Papponen
H
H
Department of Anatomy and Cell Biology, University of Oulu, PO Box 5000, FIN-90014, Finland.
Kaisto
T
T
Myllylä
V V
VV
Myllylä
R
R
Metsikkö
K
K
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D018118:Chloride Channels / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D004558:Electric Stimulation / Q000379:methods; D005260:Female; D051379:Mice; D008818:Mice, Neurologic Mutants; D008969:Molecular Sequence Data; D018485:Muscle Fibers, Skeletal / Q000737:chemistry / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012508:Sarcolemma / Q000737:chemistry / Q000502:physiology*
C086321:CLC-1 channel; D018118:Chloride Channels