Modification Of Loop 1 Affects The Nucleotide-Binding Properties Of Myo1c, The Adaptation Motor In The Inner Ear

Adamek, Nancy; Lieto-Trivedi, Alena; Dash, Sheffali; Geeves, Michael A.; Coluccio, Lynne M.

doi:10.1016/j.bpj.2008.12.3864

Cited by 1 publication

(2 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This dramatic force sensitivity enables myo1b to function as a tension-sensitive anchor, changing from a low-to a high-duty ratio motor with forces of <2 pN. Although it has been proposed that myo1c also acts as a tension sensor (10,12,45), the data presented here show that myo1c 3IQ is substantially less force-sensitive than myo1b (Fig. 2B).…”

Section: Discussioncontrasting

confidence: 43%

See 1 more Smart Citation

Myosin IC generates power over a range of loads via a new tension-sensing mechanism

Greenberg

Lin

Goldman

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

132

View full text Add to dashboard Cite

Myosin IC (myo1c), a widely expressed motor protein that links the actin cytoskeleton to cell membranes, has been associated with numerous cellular processes, including insulin-stimulated transport of GLUT4, mechanosensation in sensory hair cells, endocytosis, transcription of DNA in the nucleus, exocytosis, and membrane trafficking. The molecular role of myo1c in these processes has not been defined, so to better understand myo1c function, we utilized ensemble kinetic and single-molecule techniques to probe myo1c's biochemical and mechanical properties. Utilizing a myo1c construct containing the motor and regulatory domains, we found the force dependence of the actin-attachment lifetime to have two distinct regimes: a force-independent regime at forces <1 pN, and a highly force-dependent regime at higher loads. In this force-dependent regime, forces that resist the working stroke increase the actinattachment lifetime. Unexpectedly, the primary force-sensitive transition is the isomerization that follows ATP binding, not ADP release as in other slow myosins. This force-sensing behavior is unique amongst characterized myosins and clearly demonstrates mechanochemical diversity within the myosin family. Based on these results, we propose that myo1c functions as a slow transporter rather than a tension-sensitive anchor.is a widely expressed myosin-I isoform that has been associated with several important cellular processes, including endocytosis (1), exocytosis (2) (including insulin-stimulated GLUT4 translocation to the cell membrane; refs. 3-5), membrane ruffling (6), transcription of DNA in the nucleus (7,8), and mechanosensing in sensory hair cells (9-13). Although it is known that myo1c links cell membranes to the actin cytoskeleton (14, 15), its molecular role in these cellular processes has not been determined. For example, in its proposed role in exocytosis, it is not known if myo1c acts as a motor for transport, moving vesicles into position for plasma membrane fusion and/or as a tension-sensitive anchor that docks exocytic vesicles to the actin cytoskeleton and plasma membrane.Most members of the myosin family share the same kinetic pathway for ATP hydrolysis, in which force-generating structural changes are linked to release of inorganic phosphate and ADP, but different myosin isoforms have evolved different biochemical reaction rates and force-dependent kinetics to suit their cellular functions. For example, in myosins that are thought to act as tension-sensitive anchors, the kinetic steps that limit actomyosin detachment are highly sensitive to load. In contrast, myosins that are thought to act as transporters have actin-detachment kinetics that are less sensitive to load, allowing work to be performed over a range of forces. Thus, insight into the molecular role of myosin in the cell can be gained from evaluating the kinetic and mechanical properties of the motor.Previous biochemical analyses have shown that myo1c is a lowduty ratio motor (i.e., it spends most of its biochemical cycle detached from act...

show abstract

Section: Discussioncontrasting

confidence: 43%

“…Myo1c has been proposed to be the slow adaptation motor in sensory hair cells where it senses changes in the tension of the tip link (9)(10)(11)(12)(13)45). If this is myo1c's role, then models need to incorporate the motor's unique tension-sensing properties.…”

Section: Discussionmentioning

confidence: 99%

Myosin IC generates power over a range of loads via a new tension-sensing mechanism

Greenberg

Lin

Goldman

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

132

View full text Add to dashboard Cite

show abstract

Modification Of Loop 1 Affects The Nucleotide-Binding Properties Of Myo1c, The Adaptation Motor In The Inner Ear

Abstract: The version in the Kent Academic Repository may differ from the final published version. Users are advised to check http://kar.kent.ac.uk for the status of the paper. Users should always cite the published version of record.

Cited by 1 publication

References 47 publications

Myosin IC generates power over a range of loads via a new tension-sensing mechanism

Myosin IC generates power over a range of loads via a new tension-sensing mechanism

Contact Info

Product

Resources

About