A sarcomeric α-actinin truncated at the carboxyl end induces the breakdown of stress fibers in PtK2 cells and the formation of nemaline-like bodies and breakdown of myofibrils in myotubes

Academic Article

Abstract

  • In many nonmuscle cells, nonsarcomeric α-actinin is distributed in the dense bodies of stress fibers, adhesion plaques, and adherens junctions. In striated muscle, a sarcomeric isoform of α-actinin (s-α-actinin) is found in the Z-bands of myofibrils and subsarcolemmal adhesion plaques. To understand the role(s) of the α-actinin isoforms in the assembly and maintenance of such cytoskeletal structures, full-length or truncated s-α- actinin cDNAs were expressed in PtK2 cells and in primary skeletal myogenic cells. We found the following. (i) In transfected PtK2 cells the truncated s- α-actinin was rapidly incorporated into preexisting dense bodies, adhesion plaques, and adherens junctions. With time these structures collapsed, and the affected cells detached from the substrate. (ii) In myotubes the truncated s-α-actinin was incorporated into nascent Z-bands. Many of these progressively hypertrophied, forming nemaline-like bodies. With time the affected myofibrils fragmented, and the myotubes detached from the substrate. (iii) In both cell types the truncated s-α-actinin was significantly more disruptive of the cytoskeletal structures than the full-length molecule. (iv) Pools of 'over-expressed' full-length or truncated protein did not self- aggregate into homogeneous, amorphous complexes; rather the exogenous proteins selectively colocalized with the same cohort of cytoskeletal proteins with which the endogenous α-actinin normally associates. The similarity among the hypertrophied Z-bands in transfected myotubes, the nemaline bodies in patients with nemaline myopathies, and the streaming Z- bands seen in various muscle pathologies raises the possibility that the genetically determined nemaline bodies and the pathologically induced Z-band alterations may reflect primary and/or posttranslational modifications of s- α-actinin.
  • Authors

    Digital Object Identifier (doi)

    Author List

  • Schultheiss T; Choi J; Lin ZX; DiLullo C; Cohen-Gould L; Fischman D; Holtzer H
  • Start Page

  • 9282
  • End Page

  • 9286
  • Volume

  • 89
  • Issue

  • 19