Myosin phosphatase coordinates the levels of contractility and acetylated microtubules to ensure normal cell migration

Tuesday, October 25, 2011 — Poster Session II
Noon – 2:00 p.m.	Natcher Conference Center	NIDCR	CELLBIO-5

* FARE Award Winner

Authors

• E Joo
• K Yamada

Abstract

Although much is known about how individual cytoskeletal systems contribute to cellular locomotion, how these different systems coordinate their functions to achieve physiological migration is still poorly understood. Here we show that human fibroblasts reciprocally coordinate levels of acetylated microtubules and activity of actomyosin contraction to modulate the surface density of integrin and the progression of adhesion maturation, which dictate the migration rates of fibroblasts. Experimentally reducing contraction increased the level of acetylated microtubules. Conversely, increasing microtubule acetylation decreased cellular contraction. This inverse, reciprocal interaction between acetylated microtubules and contraction was achieved by competitive myosin phosphatase interactions with either MLC or HDAC6, which affected the activation state of either protein. This balance of contractility and acetylated microtubules controlled the surface density of the alpha5beta1 integrin, which affected adhesion maturation into fibrillar adhesions. Hyperacetylation of microtubules decreased endocytosis of the alpha5beta1 integrin and the decreased rate of migration due to hyperacetylation of microtubules was partially rescued by inhibiting the alpha5beta1 integrin. Thus, a homeostatic balance between contractility and acetylated microtubules is achieved through controlled activation and deactivation of myosin II and HDAC6, which regulates the surface density of alpha5beta1 integrin and maturation of adhesions, thereby governing the rate of cell migration.

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