Open Close
Reference
Citation
Clark, K.A., Kadrmas, J.L. (2013). Drosophila melanogaster muscle LIM protein and alpha-actinin function together to stabilize muscle cytoarchitecture: A potential role for Mlp84B in actin-crosslinking.  Cytoskeleton (Hoboken) 70(6): 304--316.
FlyBase ID
FBrf0222192
Publication Type
Research paper
Abstract

Stabilization of tissue architecture during development and growth is essential to maintain structural integrity. Because of its contractile nature, muscle is especially susceptible to physiological stresses, and has multiple mechanisms to maintain structural integrity. The Drosophila melanogaster Muscle LIM Protein (MLP), Mlp84B, participates in muscle maintenance, yet its precise mechanism of action is still controversial. Through a candidate approach, we identified α-actinin as a protein that functions with Mlp84B to ensure muscle integrity. α-actinin RNAi animals die primarily as pupae, and Mlp84B RNAi animals are adult viable. RNAi knockdown of Mlp84B and α-actinin together produces synergistic early larval lethality and destabilization of Z-line structures. We recapitulated these phenotypes using combinations of traditional loss-of-function alleles and single-gene RNAi. We observe that Mlp84B induces the formation of actin loops in muscle cell nuclei in the absence of nuclear α-actinin, suggesting Mlp84B has intrinsic actin cross-linking activity, which may complement α-actinin cross-linking activity at sites of actin filament anchorage. These results reveal a molecular mechanism for MLP stabilization of muscle and implicate reduced actin crosslinking as the primary destabilizing defect in MLP-associated cardiomyopathies. Our data support a model in which α-actinin and Mlp84B have important and overlapping functions at sites of actin filament anchorage to preserve muscle structure and function.

PubMed ID
PubMed Central ID
PMC3716849 (PMC) (EuropePMC)
Associated Information
Comments
Associated Files
Other Information
Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Cytoskeleton (Hoboken)
    Title
    Cytoskeleton (Hoboken)
    ISBN/ISSN
    1949-3584 1949-3592
    Data From Reference
    Aberrations (2)
    Alleles (7)
    Genes (4)
    Physical Interactions (2)
    Cell Lines (1)
    Transgenic Constructs (4)