Structural and functional diversity of novel coronin 1C (CRN2) isoforms in muscle.
Coronin 1C (synonyms: coronin-3, CRN2), a WD40 repeat-containing protein involved in cellular actin dynamics, is ubiquitously expressed in human tissues. Here, we report on the identification and functional characterization of two novel coronin 1C isoforms, referred to as CRN2i2 and CRN2i3, which also associate with F-actin. Analyses of the coronin 1C gene disclosed a single promoter containing binding sites for myogenic regulatory factors and an alternative first exon 1b present in intron 1, which give rise to the novel isoforms. Chromatin immunoprecipitation studies demonstrate MyoD binding to a region of the CRN2 gene, which contains a highly conserved E-box element in exon 1a. Gel-filtration assays suggest that the largest isoform 3 exists as a monomer, in contrast to isoform 1 and isoform 2 appearing as trimers. CRN2i3, which can be induced by MyoD, is exclusively expressed in well-differentiated myoblasts as well as in mature skeletal muscle tissue. In human skeletal muscle, CRN2i3 is a novel component of postsynaptic neuromuscular junctions and thin filaments of myofibrils. Together, our findings postulate a role for CRN2 isoforms in the structural and functional organization of F-actin in highly ordered protein complexes.
Xavier
Charles-Peter
CP
Center for Biochemistry, Institute of Biochemistry I, University of Cologne, Germany.
Rastetter
Raphael H
RH
Stumpf
Maria
M
Rosentreter
André
A
Müller
Rolf
R
Reimann
Jens
J
Cornfine
Susanne
S
Linder
Stefan
S
van Vliet
Vanessa
V
Hofmann
Andreas
A
Morgan
Reginald O
RO
Fernandez
Maria-Pilar
MP
Schröder
Rolf
R
Noegel
Angelika A
AA
Clemen
Christoph S
CS
D000199:Actins / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D019295:Computational Biology; D006801:Humans; D007150:Immunohistochemistry; D008840:Microfilament Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000378:metabolism; D009210:Myofibrils / Q000378:metabolism; D009469:Neuromuscular Junction / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D055503:Protein Multimerization; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000199:Actins; D008840:Microfilament Proteins; D020033:Protein Isoforms; D011993:Recombinant Fusion Proteins; C072061:coronin proteins