PMID- 10601341
OWN - NLM
STAT- MEDLINE
DCOM- 20000111
LR  - 20190508
IS  - 0021-9525 (Print)
IS  - 0021-9525 (Linking)
VI  - 147
IP  - 6
DP  - 1999 Dec 13
TI  - Vertebrate isoforms of actin capping protein beta have distinct functions In
      vivo.
PG  - 1287-98
AB  - Actin capping protein (CP) binds barbed ends of actin filaments to regulate actin
      assembly. CP is an alpha/beta heterodimer. Vertebrates have conserved isoforms of
      each subunit. Muscle cells contain two beta isoforms. beta1 is at the Z-line;
      beta2 is at the intercalated disc and cell periphery in general. To investigate
      the functions of the isoforms, we replaced one isoform with another using
      expression in hearts of transgenic mice. Mice expressing beta2 had a severe
      phenotype with juvenile lethality. Myofibril architecture was severely disrupted.
      The beta2 did not localize to the Z-line. Therefore, beta1 has a distinct
      function that includes interactions at the Z-line. Mice expressing beta1 showed
      altered morphology of the intercalated disc, without the lethality or myofibril
      disruption of the beta2-expressing mice. The in vivo function of CP is presumed
      to involve binding barbed ends of actin filaments. To test this hypothesis, we
      expressed a beta1 mutant that poorly binds actin. These mice showed both
      myofibril disruption and intercalated disc remodeling, as predicted. Therefore,
      CPbeta1 and CPbeta2 each have a distinct function that cannot be provided by the 
      other isoform. CPbeta1 attaches actin filaments to the Z-line, and CPbeta2
      organizes the actin at the intercalated discs.
FAU - Hart, M C
AU  - Hart MC
AD  - Department of Cell Biology and Physiology, Washington University School of
      Medicine, St. Louis, Missouri 63110, USA.
FAU - Cooper, J A
AU  - Cooper JA
LA  - eng
GR  - R01 GM038542/GM/NIGMS NIH HHS/United States
GR  - R01 GM038542-11/GM/NIGMS NIH HHS/United States
GR  - GM38542/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Cell Biol
JT  - The Journal of cell biology
JID - 0375356
RN  - 0 (Actin Capping Proteins)
RN  - 0 (Actin Depolymerizing Factors)
RN  - 0 (Destrin)
RN  - 0 (Microfilament Proteins)
RN  - 0 (Protein Isoforms)
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - Actin Capping Proteins
MH  - Actin Depolymerizing Factors
MH  - Animals
MH  - Cardiomyopathy, Hypertrophic/metabolism/pathology
MH  - Destrin
MH  - Fluorescent Antibody Technique
MH  - Gene Expression
MH  - Genes, Lethal/genetics
MH  - Genetic Complementation Test
MH  - Longevity
MH  - Mice
MH  - Mice, Transgenic
MH  - Microfilament Proteins/*chemistry/genetics/*metabolism
MH  - Microscopy, Electron
MH  - Mutation/genetics
MH  - Myocardium/*metabolism/pathology/ultrastructure
MH  - Myofibrils/metabolism/pathology/ultrastructure
MH  - Organ Size
MH  - Phenotype
MH  - Protein Isoforms/chemistry/genetics/metabolism
MH  - RNA, Messenger/analysis/genetics
MH  - Structure-Activity Relationship
PMC - PMC2168092
EDAT- 1999/12/22 00:00
MHDA- 1999/12/22 00:01
CRDT- 1999/12/22 00:00
PHST- 1999/12/22 00:00 [pubmed]
PHST- 1999/12/22 00:01 [medline]
PHST- 1999/12/22 00:00 [entrez]
AID - 10.1083/jcb.147.6.1287 [doi]
PST - ppublish
SO  - J Cell Biol. 1999 Dec 13;147(6):1287-98. doi: 10.1083/jcb.147.6.1287.