Primary structure and functional expression of the alpha-, beta-, gamma-, delta- and epsilon-subunits of the acetylcholine receptor from rat muscle.
The isolation and characterization of five clones carrying sequences of the alpha-, beta-, gamma-, delta- and epsilon-subunit precursors of the rat muscle acetylcholine receptor (AChR) are described. The deduced amino acid sequences indicate that these polypeptides contain 457-519 amino acids and reveal the structural characteristics common to subunits of ligand-gated ion channels. The pattern of subunit-specific mRNA levels in rat muscle shows characteristic changes during development and following denervation, suggesting that innervation of muscle reduces the expression of the alpha-, beta- and delta-subunit mRNAs, suppresses the expression of the gamma-subunit mRNA, and induces expression of epsilon-subunit mRNA. Subunit-specific cRNAs generated in vitro were injected into Xenopus laevis oocytes, resulting in the assembly of two functionally different AChR channel subtypes. The AChR gamma, composed of the alpha-, beta-, gamma- and delta-subunits, has functional properties similar to those of the native AChRs in fetal muscle. The AChR epsilon, composed of alpha-, beta-, delta- and epsilon-subunits, corresponds to the end-plate channel of the adult muscle. Thus in rat skeletal muscle the motor nerve regulates the expression of two functionally different AChR subtypes with different molecular composition by the differential expression of subunit-specific mRNAs.
Max-Planck-Institut für medizinische Forschung, Abteilung Zellphysiologie, Heidelberg, Federal Republic of Germany.
V
V
Witzemann
E
E
Stein
B
B
Barg
T
T
Konno
M
M
Koenen
W
W
Kues
M
M
Criado
M
M
Hofmann
B
B
Sakmann
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D006031:Glycosylation; D008564:Membrane Potentials; D008969:Molecular Sequence Data; D009132:Muscles / Q000378:metabolism*; D009693:Nucleic Acid Hybridization; D010766:Phosphorylation; D012313:RNA / Q000032:analysis / Q000302:isolation & purification; D051381:Rats; D011950:Receptors, Cholinergic / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D014982:Xenopus laevis / Q000378:metabolism
D011950:Receptors, Cholinergic; D012313:RNA; D004247:DNA