Nuclear myosin I regulates cell membrane tension

Abstract

Plasma membrane tension is an important feature that determines the cell shape and influences processes such as cell motility, spreading, endocytosis and exocytosis. Unconventional class 1 myosins are potent regulators of plasma membrane tension because they physically link the plasma membrane with adjacent cytoskeleton. We identified nuclear myosin 1 (NM1) - a putative nuclear isoform of myosin 1c (Myo1c) - as a new player in the field. Although having specific nuclear functions, NM1 localizes predominantly to the plasma membrane. Deletion of NM1 causes more than a 50% increase in the elasticity of the plasma membrane around the actin cytoskeleton as measured by atomic force microscopy. This higher elasticity of NM1 knock-out cells leads to 25% higher resistance to short-term hypotonic environment and rapid cell swelling. In contrast, overexpression of NM1 in wild type cells leads to an additional 30% reduction of their survival. We have shown that NM1 has a direct functional role in the cytoplasm as a dynamic linker between the cell membrane and the underlying cytoskeleton, regulating the degree of effective plasma membrane tension.

Propagating actomyosin-generated force to intercellular junction

“…We propose that one possible function of myosin-1c in mature cell monolayers is to provide sustained membrane tension beyond the initial force production step of an actomyosin II contraction. In support of our hypothesis, myosin-1 has been shown to promote the generation of resting membrane tension [55][56][57] , and plays a role in force production [41,58] and actin compression on the lateral membrane [59,60]. The interaction of myosin-1c to actin filaments can be fine-tuned by intracellular calcium.…”

Myosin-1c promotes E-cadherin tension and force-dependent recruitment of α-actinin to the epithelial cell junction

“…Consequently, myosin-1c can hold onto an actin filament longer if the actin filament is pulled. Myosin-1 has been shown to promote the generation of resting membrane tension (Dai et al, 1999;Nambiar et al, 2009;Venit et al, 2016) and facilitate actin compression on the plasma membrane (Sokac et al, 2006;Kittelberger et al, 2016). Moreover, the interaction of myosin-1c with actin can be finetuned by intracellular Ca 2+ (Lieto-Trivedi and Coluccio, 2008;Lu et al, 2015;Manceva et al, 2007;Phillips et al, 2006;Lewis et al, 2012).…”

N-terminal splicing extensions of the human MYO1C gene fine-tune the kinetics of the three full-length myosin IC isoforms

“…MYO1C 16 , although displaying specific nuclear functions, localizes to the plasma membrane. Furthermore, knock-out of MYO1C 16 has strong effects on the elasticity of the plasma membrane around the actin cytoskeleton, as determined by atomic force microscopy (24). Overall, MYO1C isoforms possess overall nearly identical structural domains and most likely are subject to similar post-translational modifications and binding to similar partners.…”

“…In the nucleus, MYO1C 16 is involved in transcription by all three RNA polymerases, mRNA maturation, chromatin remodeling, and chromosome movement (18 -23). MYO1C 16 also localizes to the cytoplasm, where, like MYO1C C , it contributes to the regulation of cell membrane tension (24). MYO1C 16 knock-out mice do not exhibit any obvious phenotype (25).…”