scholarly journals Novel functions for integrin-associated proteins revealed by myofibril attachment in Drosophila

2018 ◽  
Author(s):  
Hannah J. Green ◽  
Annabel G. M. Griffiths ◽  
Nicholas H. Brown
Keyword(s):  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Genetic Interactions ◽  
Molecular Composition ◽  
Myotendinous Junction ◽  
Membrane Anchor ◽  
Associated Proteins ◽  
Flight Muscles ◽  
Complex Architecture

AbstractWe use the myotendinous junction of Drosophila flight muscles to explore why many integrin associated proteins (IAPs) are needed and how their function is coordinated. These muscles revealed new functions for IAPs not required for viability: Focal Adhesion Kinase (FAK), RSU1, tensin and vinculin. Genetic interactions demonstrated a balance between positive and negative activities, with vinculin and tensin positively regulating adhesion, while FAK inhibits elevation of integrin activity by tensin, and RSU1 keeps PINCH activity in check. The molecular composition of myofibril termini resolves into 4 distinct layers, one of which is built by a mechanotransduction cascade: vinculin facilitates mechanical opening of filamin, which works with the Arp2/3 activator WASH to build an actin-rich layer positioned between integrins and the first sarcomere. Thus, integration of IAP activity is needed to build the complex architecture of the myotendinous junction, linking the membrane anchor to the sarcomere.Graphical abstract

scholarly journals Novel functions for integrin-associated proteins revealed by analysis of myofibril attachment in Drosophila

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Hannah J Green ◽  
Annabel GM Griffiths ◽  
Jari Ylänne ◽  
Nicholas H Brown
Keyword(s):  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Genetic Interactions ◽  
Molecular Composition ◽  
Myotendinous Junction ◽  
Membrane Anchor ◽  
Associated Proteins ◽  
Flight Muscles ◽  
Complex Architecture

We use the myotendinous junction of Drosophila flight muscles to explore why many integrin associated proteins (IAPs) are needed and how their function is coordinated. These muscles revealed new functions for IAPs not required for viability: Focal Adhesion Kinase (FAK), RSU1, tensin and vinculin. Genetic interactions demonstrated a balance between positive and negative activities, with vinculin and tensin positively regulating adhesion, while FAK inhibits elevation of integrin activity by tensin, and RSU1 keeps PINCH activity in check. The molecular composition of myofibril termini resolves into 4 distinct layers, one of which is built by a mechanotransduction cascade: vinculin facilitates mechanical opening of filamin, which works with the Arp2/3 activator WASH to build an actin-rich layer positioned between integrins and the first sarcomere. Thus, integration of IAP activity is needed to build the complex architecture of the myotendinous junction, linking the membrane anchor to the sarcomere.

Focal adhesion kinase and associated proteins

1994 ◽  
Vol 6 (5) ◽  
pp. 705-710 ◽  
Author(s):  
Michael D. Schaller ◽  
J. Thomas Parsons
Keyword(s):  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Associated Proteins

Focal Adhesion Kinase and its Associated Proteins

2019 ◽  
pp. 49-62
Author(s):  
Jill K. Slack ◽  
Judith Lacoste ◽  
J. Thomas Parsons
Keyword(s):  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Associated Proteins

Concentration of pp125 focal adhesion kinase (FAK) at the myotendinous junction

1994 ◽  
Vol 107 (6) ◽  
pp. 1485-1497
Author(s):  
L.P. Baker ◽  
D.F. Daggett ◽  
H.B. Peng
Keyword(s):  
Neuromuscular Junction ◽  
Focal Adhesion Kinase ◽  
Acetylcholine Receptor ◽  
Focal Adhesion ◽  
Cultured Cells ◽  
Muscle Cells ◽  
Relative Molecular Mass ◽  
Myotendinous Junction ◽  
Receptor Clusters

Focal adhesion kinase is a recently characterized tyrosine kinase that is concentrated at focal contacts in cultured cells. It is thought to play an important role in the regulation of the integrin-based signal transduction mechanism involved in the assembly of this membrane specialization. In this study, we examined the immunocytochemical distribution of focal adhesion kinase in Xenopus skeletal muscle and its role in the formation of two sarcolemmal specializations, the myotendinous junction and the neuromuscular junction, using a monoclonal antibody (2A7) against this protein. Immunoprecipitation of Xenopus embryonic tissues with this antibody demonstrated a single band at a relative molecular mass of 116 kDa. A distinct concentration of immunolabeling for focal adhesion kinase was observed at the myotendinous junction of muscle fibers in vivo. At this site, the labeling for this protein is correlated with an accumulation of phosphotyrosine immunolabeling. Focal adhesion kinase was not concentrated at the neuromuscular junction in muscle cells either in vivo or in vitro. However, it was localized at spontaneously formed acetylcholine receptor clusters in cultured Xenopus myotomal muscle cells, although its distribution was not exactly congruent with that of the receptors. In these cells, the accumulation focal adhesion kinase was induced by polystyrene microbeads. In addition, beads also induce the formation of acetylcholine receptor clusters and myotendinous junction-like specializations. By following the appearance of the focal adhesion kinase relative to the formation of these sarcolemmal specializations at bead-muscle contacts in cultured muscle cells, we conclude that the accumulation of this protein was in pace with the development of the myotendinous junction, but occurred well after the clustering of acetylcholine receptors. These results suggest that focal adhesion kinase may be involved in the development and/or maintenance of the myotendinous junction through an integrin-based signaling system. Although it can accumulate at acetylcholine receptor clusters formed in culture, it does not appear to be involved in the development of the neuromuscular junction.

scholarly journals Mechanosensitive tyrosine phosphorylation of paxillin and focal adhesion kinase in tracheal smooth muscle

1999 ◽  
Vol 276 (1) ◽  
pp. C250-C258 ◽  
Author(s):  
Dachun Tang ◽  
Dolly Mehta ◽  
Susan J. Gunst
Keyword(s):  
Smooth Muscle ◽  
Focal Adhesion Kinase ◽  
Tyrosine Phosphorylation ◽  
Focal Adhesion ◽  
Cell Structure ◽  
Muscle Length ◽  
Tracheal Smooth Muscle ◽  
Protein Activation ◽  
Associated Proteins

We investigated the role of the integrin-associated proteins focal adhesion kinase (FAK) and paxillin as mediators of mechanosensitive signal transduction in tracheal smooth muscle. In muscle strips contracted isometrically with ACh, we observed higher levels of tyrosine phosphorylation of FAK and paxillin at the optimal muscle length ( L o) than at shorter muscle lengths of 0.5 or 0.75 L o. Paxillin phosphorylation was also length sensitive in muscles activated by K+ depolarization and adjusted rapidly to changes in muscle length imposed after contractile activation by either ACh or K+depolarization. Ca2+ depletion did not affect the length sensitivity of paxillin and FAK phosphorylation in muscles activated with ACh, indicating that the mechanotransduction process can be mediated by a Ca2+-independent pathway. Since Ca2+-depleted muscles do not generate significant active tension, this suggests that the mechanotransduction mechanism is sensitive to muscle length rather than tension. We conclude that FAK and paxillin participate in an integrin-mediated mechanotransduction process in tracheal smooth muscle. We propose that this pathway may initiate alterations in smooth muscle cell structure and contractility via the remodeling of actin filaments and/or via the mechanosensitive regulation of signaling molecules involved in contractile protein activation.

Early signalling events of autophagy

2013 ◽  
Vol 55 ◽  
pp. 1-15 ◽  
Author(s):  
Laura E. Gallagher ◽  
Edmond Y.W. Chan
Keyword(s):  
Protein Kinase ◽  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Mammalian Cells ◽  
Mammalian Target Of Rapamycin ◽  
Interacting Protein ◽  
The Core ◽  
Autophagy Gene ◽  
Autophagy Induction ◽  
Cellular Pathways

Autophagy is a conserved cellular degradative process important for cellular homoeostasis and survival. An early committal step during the initiation of autophagy requires the actions of a protein kinase called ATG1 (autophagy gene 1). In mammalian cells, ATG1 is represented by ULK1 (uncoordinated-51-like kinase 1), which relies on its essential regulatory cofactors mATG13, FIP200 (focal adhesion kinase family-interacting protein 200 kDa) and ATG101. Much evidence indicates that mTORC1 [mechanistic (also known as mammalian) target of rapamycin complex 1] signals downstream to the ULK1 complex to negatively regulate autophagy. In this chapter, we discuss our understanding on how the mTORC1–ULK1 signalling axis drives the initial steps of autophagy induction. We conclude with a summary of our growing appreciation of the additional cellular pathways that interconnect with the core mTORC1–ULK1 signalling module.

Sign in / Sign up

Export Citation Format

Share Document