Alp/Enigma Family Proteins Cooperate in Z-Disc Formation and Myofibril Assembly

The drosophila alp/enigma family protein zasp52 localizes to myotendinous junctions and z-discs. it is required for terminal muscle differentiation and muscle attachment. its vertebrate ortholog zasp/cypher also localizes to z-discs,interacts with α-actinin through its pdz domain,and is involved in z-disc maintenance. human mutations in zasp cause myopathies and cardiomyopathies. here we show that drosophila zasp52 is one of the earliest markers of z-disc assembly,and we use a zasp52-gfp fusion to document myofibril assembly by live imaging. we demonstrate that zasp52 is required for adult z-disc stability and pupal myofibril assembly. in addition,we show that two closely related proteins,zasp66 and the newly identified zasp67,are also required for adult z-disc stability and are participating with zasp52 in z-disc assembly resulting in more severe,synergistic myofibril defects in double mutants. zasp52 and zasp66 directly bind to α-actinin,and they can also form a ternary complex. our results indicate that alp/enigma family members cooperate in z-disc assembly and myofibril formation; and we propose,based on sequence analysis,a novel class of pdz domain likely involved in α-actinin binding. © 2013 katzemich et al.