Mua-6, a gene required for tissue integrity in Caenorhabditis elegans, encodes a cytoplasmic intermediate filament

Abstract

Locomotion in Caenorhabditis elegans requires force transmission through a network of proteins linking the skeletal muscle, via an intervening basal lamina and epidermis (hypodermis), to the cuticle. Mutations in mua-6 result in hypodermal rupture, muscle detachment from the bodywall, and progressive paralysis. It is shown that mua-6 encodes the cytoplasmic intermediate filament (cIF) A2 protein and that a MUA-6/IFA-2::GFP fusion protein that rescues the presumptive mua-6 null allele localizes to hypodermal hemidesmosomes. This result is consistent with what is known about the function of cIFs in vertebrates. Although MUA-6/IFA-2 is expressed embryonically, and plays an essential postembryonic role in tissue integrity, it is not required for embryonic development of muscle-cuticle linkages nor for the localization of other cIFs or hemidesmosome-associated proteins in the embryo. Finally, the molecular lesion in the mua-6(rh85) allele suggests that the head domain of the MUA-6/IFA-2 is dispensable for its function.

Intermediate filaments in Caenorhabditis elegans

“…We think that this and the fact that all IFCs, IFDs as well as IFP-1 and IFB-2 are present in the intestinal apical terminal web justify a common grouping. The IF-rich terminal web is a characteristic feature of the subapical region of adluminal metazoan intestinal cells [Hirokawa et al, 1982] consisting of a complex mesh of various cytoskeletal and [Karabinos et al, 2003] Early larval Essential for viability after L1 [Karabinos et al, 2001] IFA-1b: amphids, c some neurons, c pharyngeal-intestinal valve, c vulva, c rectum c [Karabinos et al, 2001[Karabinos et al, , 2003] IFA-2 (5 MUA-6) Hypodermis, b,c amphids, c uterus, b,c vulva, c rectum c [Hapiak et al, 2003;Karabinos et al, 2002Karabinos et al, , 2003 Early larval Hypodermal integrity, attachment of muscles to the body wall [Karabinos et al, 2001;Hapiak et al, 2003] IFA-3…”

“…The contribution of IFA-2, IFA-3, and IFB-1 to epidermal morphogenesis, elongation, and muscle attachment has been emphasized in this context lending strong support for a crucial mechanical function of IFs [Plenefisch et al, 2000;Karabinos et al, 2001Karabinos et al, , 2004Hapiak et al, 2003;Woo et al, 2004].…”

TheC. elegansUNC-23 protein, a member of the BCL-2-associated athanogene (BAG) family of chaperone regulators, interacts with HSP-1 to regulate cell attachment and maintain hypodermal integrity

“…12, [14][15][16][17][18][19][20] Mutations affecting the unc-23 gene were first isolated in a forward genetic screen designed to identify animals with visible mutant phenotypes. 21 Among the original 619 mutants that were identified, only Unc-23 mutant animals exhibited a progressive dystrophy of the head musculature resulting in a bent-head phenotype.…”

Recent Advances in Elucidating Nematode Moulting – Prospects of Using Oesophagostomum dentatum as a Model

“…during and after moulting and/or exsheathment. The downregulation of the structural proteins ACT, IFB, TNT and TPM in moulting-inhibited O. dentatum L3s and/or their overexpression in L3 during exsheathment indicate their role(s) in movement to shed their old cuticle during ecdysis, as they are known to be linked to myofibril assembly and muscle contraction (Hapiak et al, 2003;Krause et al, 1989;Myers et al, 1996;Ohtsuki et al, 1986). Several of the identified proteins, including 14-3-3 protein, GDI, RACK-1, TTL-5 and VDAC, have diverse roles in various protein interactions and/or in fulfilling pathway regulatory functions.…”