What is the role of microtubules in mechanotransduction?2018-02-06T10:30:32+00:00

What is the role of microtubules in mechanotransduction?

Microtubules exist in all cells, however their influence in the mechanotransduction of mechanical stimuli has been described at length in cardiac striated muscle [1] and as such these findings are summarised here:

Mechanical stimuli also affect microtubule formation and proliferation. This has been observed where passive stretching of cardiac muscle was shown to directly affect microtubule formation. In this case, tubulin mRNA and protein levels were shown to be upregulated in response to the passive stretching of neonatal cardiac myocytes [2]. These results were supported by findings of increased proliferation of microtubules following centrifugal force stretch of ventricular myocytes isolated from neonatal rats [3].

Intracellular Viscosity and Myocardiac Pressure Overload

Microtubule proliferation has also been shown to increase the intracellular viscosity of myoctyes and impede sarcomere shortening, which is required to maintain contractility of the cardiac muscle [4]. Changes to these viscoelasticitic properties have been demonstrated in a number of in vitro experiments where physical stresses or the use of agents that selectively disrupt or promote microtubule formation, are applied to cells. In one such case, hypertensive ventricular myocytes were found to be stiffer and more viscous than normotensive ventricular myocytes, a property that was was removed following treatment with colchicine (an inhibitor of microtubule formation) [5].

It has been well established that myocardial pressure overloading, which results from ventricular hypertrophy, is associated with the loss of cardiac contractility in patients with heart failure [4]. Cooper et al attributed this to an increase in the density of microtubules within cardiac myocytes, where a viscous load is placed on the myofilaments and subsequently impedes sarcomere shortening. In support of their hypothesis, it was shown that treatment with microtubule depolymerizing agents such as colchicine increased contractility [4].

Impact of Microtubules on the Electrical Activity of the Heart

It has also been reported that mechanotransduction of mechanical stimuli through the microtubule network affects the electrical activity of the heart [1]. This remains controversial however, with different studies reporting opposing findings depending on the model used. For example whilst colchicine treatment (and subsequent microtubule depolymerization) was found to promote arrhythmias in a swine model [6], it had no effect in rabbits [7].

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References

  1. White E. Mechanical modulation of cardiac microtubules. Pflugers Arch. 2011; 462(1):177-84. [PMID: 21487691]
  2. Watson PA, Hannan R, Carl LL, and Giger KE. Contractile activity and passive stretch regulate tubulin mRNA and protein content in cardiac myocytes. Am. J. Physiol. 1996; 271(2 Pt 1):C684-9. [PMID: 8770010]
  3. Yutao X, Geru W, Xiaojun B, Tao G, and Aiqun M. Mechanical stretch-induced hypertrophy of neonatal rat ventricular myocytes is mediated by beta(1)-integrin-microtubule signaling pathways. Eur. J. Heart Fail. 2005; 8(1):16-22. [PMID: 16198630]
  4. Cooper G. Cytoskeletal networks and the regulation of cardiac contractility: microtubules, hypertrophy, and cardiac dysfunction. Am. J. Physiol. Heart Circ. Physiol. 2006; 291(3):H1003-14. [PMID: 16679401]
  5. Tagawa H, Wang N, Narishige T, Ingber DE, Zile MR, and Cooper G. Cytoskeletal mechanics in pressure-overload cardiac hypertrophy. Circ. Res. 1997; 80(2):281-9. [PMID: 9012750]
  6. Madias C, Maron BJ, Supron S, Estes NAM, and Link MS. Cell membrane stretch and chest blow-induced ventricular fibrillation: commotio cordis. J. Cardiovasc. Electrophysiol. 2008; 19(12):1304-9. [PMID: 18691236]
  7. Dick DJ, and Lab MJ. Mechanical modulation of stretch-induced premature ventricular beats: induction of mechanoelectric adaptation period. Cardiovasc. Res. 1998; 38(1):181-91. [PMID: 9683920]