Still Heart Encodes a Structural HMT, SMYD1b, with Chaperone-Like Function during Fast Muscle Sarcomere Assembly

Kendal Prill,David B Pilgrim,Serene L Wohlgemuth,Pamela Windsor Reid,Eric A Shelden

doi:10.1371/journal.pone.0142528

Abstract

The vertebrate sarcomere is a complex and highly organized contractile structure whose assembly and function requires the coordination of hundreds of proteins. Proteins require proper folding and incorporation into the sarcomere by assembly factors, and they must also be maintained and replaced due to the constant physical stress of muscle contraction. Zebrafish mutants affecting muscle assembly and maintenance have proven to be an ideal tool for identification and analysis of factors necessary for these processes. The still heart mutant was identified due to motility defects and a nonfunctional heart. The cognate gene for the mutant was shown to be smyd1b and the still heart mutation results in an early nonsense codon. SMYD1 mutants show a lack of heart looping and chamber definition due to a lack of expression of heart morphogenesis factors gata4, gata5 and hand2. On a cellular level, fast muscle fibers in homozygous mutants do not form mature sarcomeres due to the lack of fast muscle myosin incorporation by SMYD1b when sarcomeres are first being assembled (19hpf), supporting SMYD1b as an assembly protein during sarcomere formation.

Highlights

The sarcomere is a complex and highly organized structure where distinct protein filaments rely on the involvement and coordination of hundreds of other proteins for proper patterning, assembly and maintenance
To determine whether SMYD1b is playing a role in muscle development as a histone methyltransferase (HMT), responsible for myosin expression, or a myosin chaperone that is required for assembly and maintenance of the sarcomere, we examined myosin expression and incorporation into the doi:10.1371/journal.pone.0142528.g002
We demonstrate that the histone methyltransferase, SMYD1b, is a chaperone-like assembly protein that is crucial to the assembly of the sarcomere with regards to fast but not slow muscle myosin in striated muscle

Summary

Introduction

The sarcomere is a complex and highly organized structure where distinct protein filaments rely on the involvement and coordination of hundreds of other proteins for proper patterning, assembly and maintenance. Sarcomere proteins fall into three broad categories including contractile proteins, such as actin and myosin; structural attachment and anchoring components, such as integrins, α-actinin and myomesin, and patterning and folding chaperones such as Hsp90 [1,2,3]. While the function and activity of these proteins is well established in the mature sarcomere, the mechanisms by which the sarcomere proteins are assembled and initially patterned as the myocyte differentiates are still a matter of conjecture. The Still Heart Mutant Affects Zebrafish Myogenesis

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Conclusion