#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Sarcomere Formation Occurs by the Assembly of Multiple Latent Protein Complexes


The stereotyped striation of myofibrils is a conserved feature of muscle organization that is critical to its function. Although most components that constitute the basic myofibrils are well-characterized biochemically and are conserved across the animal kingdom, the mechanisms leading to the precise assembly of sarcomeres, the basic units of myofibrils, are poorly understood. To gain insights into this process, we investigated the functional relationships of sarcomeric protein complexes. Specifically, we systematically analyzed, using either RNAi in primary muscle cells or available genetic mutations, the organization of myofibrils in Drosophila muscles that lack one or more sarcomeric proteins. Our study reveals that the thin and thick filaments are mutually dependent on each other for striation. Further, the tension sensor complex comprised of zipper/Zasp/α-actinin is involved in stabilizing the sarcomere but not in its initial formation. Finally, integrins appear essential for the interdigitation of thin and thick filaments that occurs prior to striation. Thus, sarcomere formation occurs by the coordinated assembly of multiple latent protein complexes, as opposed to sequential assembly.


Vyšlo v časopise: Sarcomere Formation Occurs by the Assembly of Multiple Latent Protein Complexes. PLoS Genet 6(11): e32767. doi:10.1371/journal.pgen.1001208
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1001208

Souhrn

The stereotyped striation of myofibrils is a conserved feature of muscle organization that is critical to its function. Although most components that constitute the basic myofibrils are well-characterized biochemically and are conserved across the animal kingdom, the mechanisms leading to the precise assembly of sarcomeres, the basic units of myofibrils, are poorly understood. To gain insights into this process, we investigated the functional relationships of sarcomeric protein complexes. Specifically, we systematically analyzed, using either RNAi in primary muscle cells or available genetic mutations, the organization of myofibrils in Drosophila muscles that lack one or more sarcomeric proteins. Our study reveals that the thin and thick filaments are mutually dependent on each other for striation. Further, the tension sensor complex comprised of zipper/Zasp/α-actinin is involved in stabilizing the sarcomere but not in its initial formation. Finally, integrins appear essential for the interdigitation of thin and thick filaments that occurs prior to striation. Thus, sarcomere formation occurs by the coordinated assembly of multiple latent protein complexes, as opposed to sequential assembly.


Zdroje

1. AhmadF

SeidmanJG

SeidmanCE

2005 The genetic basis for cardiac remodeling. Annu Rev Genomics Hum Genet 6 185 216

2. DalkilicI

KunkelLM

2003 Muscular dystrophies: genes to pathogenesis. Curr Opin Genet Dev 13 231 238

3. HoltzerH

HijikataT

LinZX

ZhangZQ

HoltzerS

1997 Independent assembly of 1.6 microns long bipolar MHC filaments and I-Z-I bodies. Cell Struct Funct 22 83 93

4. LinZ

LuMH

SchultheissT

ChoiJ

HoltzerS

1994 Sequential appearance of muscle-specific proteins in myoblasts as a function of time after cell division: evidence for a conserved myoblast differentiation program in skeletal muscle. Cell Motil Cytoskeleton 29 1 19

5. LuMH

DiLulloC

SchultheissT

HoltzerS

MurrayJM

1992 The vinculin/sarcomeric-alpha-actinin/alpha-actin nexus in cultured cardiac myocytes. J Cell Biol 117 1007 1022

6. RheeD

SangerJM

SangerJW

1994 The premyofibril: evidence for its role in myofibrillogenesis. Cell Motil Cytoskeleton 28 1 24

7. LoRussoSM

RheeD

SangerJM

SangerJW

1997 Premyofibrils in spreading adult cardiomyocytes in tissue culture: evidence for reexpression of the embryonic program for myofibrillogenesis in adult cells. Cell Motil Cytoskeleton 37 183 198

8. EhlerE

RothenBM

HammerleSP

KomiyamaM

PerriardJC

1999 Myofibrillogenesis in the developing chicken heart: assembly of Z-disk, M-line and the thick filaments. J Cell Sci 112 Pt 10 1529 1539

9. GregorioCC

GranzierH

SorimachiH

LabeitS

1999 Muscle assembly: a titanic achievement? Curr Opin Cell Biol 11 18 25

10. SparrowJC

SchockF

2009 The initial steps of myofibril assembly: integrins pave the way. Nat Rev Mol Cell Biol 10 293 298

11. BrownNH

1994 Null mutations in the alpha PS2 and beta PS integrin subunit genes have distinct phenotypes. Development 120 1221 1231

12. LeeM

CramEJ

ShenB

SchwarzbauerJE

2001 Roles for beta(pat-3) integrins in development and function of Caenorhabditis elegans muscles and gonads. J Biol Chem 276 36404 36410

13. SchwanderM

LeuM

StummM

DorchiesOM

RueggUT

2003 Beta1 integrins regulate myoblast fusion and sarcomere assembly. Dev Cell 4 673 685

14. VolkT

FesslerLI

FesslerJH

1990 A role for integrin in the formation of sarcomeric cytoarchitecture. Cell 63 525 536

15. BloorJW

BrownNH

1998 Genetic analysis of the Drosophila alphaPS2 integrin subunit reveals discrete adhesive, morphogenetic and sarcomeric functions. Genetics 148 1127 1142

16. BaiJ

BinariR

NiJQ

VijayakanthanM

LiHS

2008 RNA interference screening in Drosophila primary cells for genes involved in muscle assembly and maintenance. Development 135 1439 1449

17. BaiJ

SeppKJ

PerrimonN

2009 Culture of Drosophila primary cells dissociated from gastrula embryos and their use in RNAi screening. Nat Protoc 4 1502 1512

18. BaiJ

HartwigJH

PerrimonN

2007 SALS, a WH2-domain-containing protein, promotes sarcomeric actin filament elongation from pointed ends during Drosophila muscle growth. Dev Cell 13 828 842

19. SchultheissT

LinZX

LuMH

MurrayJ

FischmanDA

1990 Differential distribution of subsets of myofibrillar proteins in cardiac nonstriated and striated myofibrils. J Cell Biol 110 1159 1172

20. Van der VenPF

EhlerE

PerriardJC

FurstDO

1999 Thick filament assembly occurs after the formation of a cytoskeletal scaffold. J Muscle Res Cell Motil 20 569 579

21. SangerJW

KangS

SiebrandsCC

FreemanN

DuA

2005 How to build a myofibril. J Muscle Res Cell Motil 26 343 354

22. O'DonnellPT

BernsteinSI

1988 Molecular and ultrastructural defects in a Drosophila myosin heavy chain mutant: differential effects on muscle function produced by similar thick filament abnormalities. J Cell Biol 107 2601 2612

23. BernsteinSI

O'DonnellPT

CrippsRM

1993 Molecular genetic analysis of muscle development, structure, and function in Drosophila. Int Rev Cytol 143 63 152

24. NishiiK

MorimotoS

MinakamiR

MiyanoY

HashizumeK

2008 Targeted disruption of the cardiac troponin T gene causes sarcomere disassembly and defects in heartbeat within the early mouse embryo. Dev Biol 322 65 73

25. NongthombaU

ClarkS

CumminsM

AnsariM

StarkM

2004 Troponin I is required for myofibrillogenesis and sarcomere formation in Drosophila flight muscle. J Cell Sci 117 1795 1805

26. SehnertAJ

HuqA

WeinsteinBM

WalkerC

FishmanM

2002 Cardiac troponin T is essential in sarcomere assembly and cardiac contractility. Nat Genet 31 106 110

27. HitchcockSE

1975 Regulation of muscle contraction: bindings of troponin and its components to actin and tropomyosin. Eur J Biochem 52 255 263

28. PelletierL

O'TooleE

SchwagerA

HymanAA

Muller-ReichertT

2006 Centriole assembly in Caenorhabditis elegans. Nature 444 619 623

29. BloorJW

KiehartDP

2001 zipper Nonmuscle myosin-II functions downstream of PS2 integrin in Drosophila myogenesis and is necessary for myofibril formation. Dev Biol 239 215 228

30. JaniK

SchockF

2007 Zasp is required for the assembly of functional integrin adhesion sites. J Cell Biol 179 1583 1597

31. ClarkKA

BlandJM

BeckerleMC

2007 The Drosophila muscle LIM protein, Mlp84B, cooperates with D-titin to maintain muscle structural integrity. J Cell Sci 120 2066 2077

32. RoperK

MaoY

BrownNH

2005 Contribution of sequence variation in Drosophila actins to their incorporation into actin-based structures in vivo. J Cell Sci 118 3937 3948

33. LittlefieldR

FowlerVM

1998 Defining actin filament length in striated muscle: rulers and caps or dynamic stability? Annu Rev Cell Dev Biol 14 487 525

34. FyrbergC

KetchumA

BallE

FyrbergE

1998 Characterization of lethal Drosophila melanogaster alpha-actinin mutants. Biochem Genet 36 299 310

35. HakedaS

EndoS

SaigoK

2000 Requirements of Kettin, a giant muscle protein highly conserved in overall structure in evolution, for normal muscle function, viability, and flight activity of Drosophila. J Cell Biol 148 101 114

36. ZhangY

FeatherstoneD

DavisW

RushtonE

BroadieK

2000 Drosophila D-titin is required for myoblast fusion and skeletal muscle striation. J Cell Sci 113 Pt 17 3103 3115

37. Pack-ChungE

KurshanPT

DickmanDK

SchwarzTL

2007 A Drosophila kinesin required for synaptic bouton formation and synaptic vesicle transport. Nat Neurosci 10 980 989

38. NewmanSMJr

WrightTR

1981 A histological and ultrastructural analysis of developmental defects produced by the mutation, lethal(1)myospheroid, in Drosophila melanogaster. Dev Biol 86 393 402

39. PerkinsAD

EllisSJ

AsghariP

ShamsianA

MooreED

Integrin-mediated adhesion maintains sarcomeric integrity. Dev Biol 338 15 27

40. SchusterCM

DavisGW

FetterRD

GoodmanCS

1996 Genetic dissection of structural and functional components of synaptic plasticity. I. Fasciclin II controls synaptic stabilization and growth. Neuron 17 641 654

41. NiJQ

MarksteinM

BinariR

PfeifferB

LiuLP

2008 Vector and parameters for targeted transgenic RNA interference in Drosophila melanogaster. Nat Methods 5 49 51

42. BernsteinSI

FyrbergEA

DonadyJJ

1978 Isolation and partial characterization of Drosophila myoblasts from primary cultures of embryonic cells. J Cell Biol 78 856 865

Štítky
Genetika Reprodukčná medicína

Článok vyšiel v časopise

PLOS Genetics


2010 Číslo 11
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Aktuální možnosti diagnostiky a léčby litiáz
nový kurz
Autori: MUDr. Tomáš Ürge, PhD.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#