Molecular Structure of Sarcomere-to-Membrane Attachment at M-Lines in C. elegans Muscle

Figure 2

A protein interaction matrix for M-lines in C. elegans striated muscle. The myofilament lattice is located close to the surface and anchored by M-lines and dense bodies to the muscle cell membrane. At these attachment structures, UNC-52 (perlecan) is located in the ECM, and by homology is likely to interact with an integrin 𝛼𝛽 heterodimer (PAT-2 and PAT-3). Inside the muscle cell, the cytoplasmic tail of PAT-3 (𝛽 integrin) is associated with a complex of four conserved proteins [UNC-112 (Kindlin), PAT-4 (ILK), PAT-6 (actopaxin), UNC-97 (PINCH)]. UNC-95 is also found at both M-lines and dense bodies. At M-lines, specific proteins link UNC-97 (PINCH) to myosin heavy chains (MHC A). These are UNC-98, LIM-9 (FHL) and UNC-96, LIM-8, and UNC-95 and LIM-8. UNC-98, UNC-96 and LIM-8 have all been shown to interact with portions of the rod domain of MHC A. LIM-9 links to the giant protein UNC-89 (obscurin) and to the phosphatase SCPL-1 (SCP). Additionally, UNC-98 and UNC-96 interact with UNC-15 (paramyosin) and to CSN-5 (COP9 signalosome component), but these interactions occur outside the M-line. The box on the right indicates that there are four more proteins that have been reported to reside at the M-line (Ce Talin, HSP25, ZYX-1 (zyxin), and UNC-82 (ARK5/SNARK)), but these have not yet been connected with components of the interaction matrix. Lines indicate interactions that were identified by 2-hybrid screens and later shown to occur with purified proteins in vitro. All proteins indicated have been localized to M-lines by specific antibodies and/or GFP fusions. References for all the interactions have been cited in the text except for the LIM-8/UNC-95 interaction (A. Simionescu, H. Qadota, and G. Benian, unpub. data).