<i>Caenorhabditis elegans</i>UNC-98, a C2H2 Zn Finger Protein, Is a Novel Partner of UNC-97/PINCH in Muscle Adhesion Complexes

Mercer, Kristina B.; Flaherty, Denise B.; Miller, Rachel K.; Qadota, Hiroshi; Tinley, Tina L.; Moerman, Donald G.; Benian, Guy M.

doi:10.1091/mbc.e02-10-0676

Cited by 57 publications

(101 citation statements)

References 54 publications

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“…Consistent with this perspective, a recently published crystal structure of LIM1 of PINCH bound to the ANKR domain of ILK confirms that human PINCH Q40 is a key residue in maintaining the PINCH-ILK interaction, and highlights that LIM1 of PINCH undergoes a conformational 'twist' upon binding to ILK that could create docking sites for additional partners (Chiswell et al, 2008;Yang et al, 2009). Several studies have identified novel binding partners for LIM1 of PINCH in C. elegans and in human cultured podocytes (Mercer et al, 2003;Qadota et al, 2007;Wang et al, 2011). However, additional research is required to assess the conservation of these PINCH-LIM1 binding partners in other organisms, as well as any potential roles they may have in PINCH localization and integrin effector function.…”

Section: Requirements For Pinch and Ilk Localization At Muscle Attachmentioning

confidence: 99%

A critical role for Ras Suppressor-1 (RSU-1) revealed when PINCH-Integrin-linked Kinase (ILK) binding is disrupted

Elias

Pronovost

Cahill

et al. 2012

Journal of Cell Science

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Summary PINCH, integrin-linked kinase (ILK) and Ras suppressor-1 (RSU-1) are molecular scaffolding proteins that form a physical complex downstream of integrins, and have overlapping roles in cellular adhesion. In Drosophila, PINCH and ILK colocalize in cells and have indistinguishable functions in maintaining wing adhesion and integrin to actin linkage in the muscle. We sought to determine whether the direct physical interaction between PINCH and ILK was essential for their functions using transgenic flies expressing a version of PINCH with a point mutation that disrupts ILK binding (PINCH Q38A ). We demonstrate that the PINCH-ILK interaction is not required for viability, for integrin-mediated adhesion of the wing or muscle, or for maintaining appropriate localization or levels of either PINCH or ILK. These results suggest alternative modes for PINCH localization, stabilization and linkage to the actin cytoskeleton that are independent of a direct interaction with ILK. Furthermore, we identified a synthetic lethality in flies carrying both the PINCH Q38A mutation and a null mutation in the gene encoding RSU-1. This lethality does not result from PINCH mislocalization or destabilization, and illustrates a novel compensatory role for RSU-1 in maintaining viability in flies with compromised PINCH-ILK binding. Taken together, this work highlights the existence of redundant mechanisms in adhesion complex assembly that support integrin function in vivo.

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Section: Requirements For Pinch and Ilk Localization At Muscle Attachmentioning

confidence: 99%

A critical role for Ras Suppressor-1 (RSU-1) revealed when PINCH-Integrin-linked Kinase (ILK) binding is disrupted

Elias

Pronovost

Cahill

et al. 2012

Journal of Cell Science

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“…Similarly, UNC-97 binds PAT-4 in yeast two-hybrid assays and is recruited to dense bodies and M-lines by PAT-4 (Hobert et al, 1999). UNC-97 also interacts with UNC-98, a C2H2 Zn-finger protein that localizes to M-lines (and possibly dense bodies) and to the nucleus (Mercer et al, 2003). UNC-98 might be involved in maintaining muscle structure, although the underlying mechanisms are not understood.…”

Section: Maintaining Integrity Of Dense Bodies and M-linesmentioning

confidence: 99%

Sticky worms: adhesion complexes inC. elegans

Cox

Hardin

2004

Journal of Cell Science

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Caenorhabditis elegans is a powerful model system for investigating the establishment, regulation and function of adhesive structures in vivo. C. elegans has several adhesion complexes related to those in vertebrates. These include: (1) epithelial apical junctions, which have features of both adherens and tight junctions; (2) dense bodies, which are muscle-attachment structures similar to focal adhesions; (3) fibrous organelles, which resemble hemidesmosomes and mediate mechanical coupling between tissues; and (4) a putative dystrophin-glycoprotein complex that has potential roles in muscle function and embryogenesis. Recent work has increased our understanding of these structures and has given new insights into the functions of their vertebrate counterparts.

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“…The significance of the nuclear UNC-82::GFP signal ( Figure 3D) is not known, but is seen with both wild-type UNC-82::GFP and E424K::GFP. Interestingly, nuclear localization has also been reported for the zinc-finger-containing M-line protein UNC-98/ZnF (Mercer et al 2003). The mammalian UNC-82 orthologs exhibit nuclear localization under conditions of stress (Kuga et al 2008;Hou et al 2011).…”

Section: Mutant Unc-82 E424k Colocalizes With Abnormal Paramyosin Accmentioning

confidence: 81%

“…Mouse monoclonal antibodies 5/6 (1:500 dilution), 5/8 (1:500 dilution), 5/23 (1:200 dilution), and rabbit polyclonal antibody EU131 (1:200) were used for immunofluorescence localization of myosin A, myosin B, paramyosin, and UNC-98, respectively (Miller et al1983;Mercer et al 2003). Rabbit and mouse anti-GFP antibodies from Jackson ImmunoResearch Laboratories (West Grove, PA) were used at 1:250 dilution.…”

Section: Microscopymentioning

confidence: 99%

The Role of the UNC-82 Protein Kinase in Organizing Myosin Filaments in Striated Muscle ofCaenorhabditis elegans

Schiller¹,

Duchesneau²,

Lane³

et al. 2017

Genetics

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We study the mechanisms that guide the formation and maintenance of the highly ordered actin-myosin cytoskeleton in striated muscle. The UNC-82 kinase of Caenorhabditis elegans is orthologous to mammalian kinases ARK5/NUAK1 and SNARK/ NUAK2. UNC-82 localizes to the M-line, and is required for proper organization of thick filaments, but its substrate and mechanism of action are unknown. Antibody staining of three mutants with missense mutations in the UNC-82 catalytic domain revealed muscle structure that is less disorganized than in the null unc-82(0), but contained distinctive ectopic accumulations not found in unc-82(0). These accumulations contain paramyosin and myosin B, but lack myosin A and myosin A-associated proteins, as well as proteins of the integrin-associated complex. Fluorescently tagged missense mutant protein UNC-82 E424K localized normally in wild type; however, in unc-82(0), the tagged protein was found in the ectopic accumulations, which we also show to label with recently synthesized paramyosin. Recruitment of wild-type UNC-82::GFP to aggregates of differing protein composition in five muscle-affecting mutants revealed that colocalization of UNC-82 and paramyosin does not require UNC-96, UNC-98/ZnF, UNC-89/obscurin, CSN-5, myosin A, or myosin B individually. Dosage effects in paramyosin mutants suggest that UNC-82 acts as part of a complex, in which its stoichiometric relationship with paramyosin is critical. UNC-82 dosage affects muscle organization in the absence of paramyosin, perhaps through myosin B. We present evidence that the interaction of UNC-98/ZnF with myosin A is independent of UNC-82, and that UNC-82 acts upstream of UNC-98/ZnF in a pathway that organizes paramyosin during thick filament assembly.

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Caenorhabditis elegansUNC-98, a C2H2 Zn Finger Protein, Is a Novel Partner of UNC-97/PINCH in Muscle Adhesion Complexes

Cited by 57 publications

References 54 publications

A critical role for Ras Suppressor-1 (RSU-1) revealed when PINCH-Integrin-linked Kinase (ILK) binding is disrupted

A critical role for Ras Suppressor-1 (RSU-1) revealed when PINCH-Integrin-linked Kinase (ILK) binding is disrupted

Sticky worms: adhesion complexes inC. elegans

The Role of the UNC-82 Protein Kinase in Organizing Myosin Filaments in Striated Muscle ofCaenorhabditis elegans

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