Myo1c Binds Phosphoinositides Through a Putative Pleckstrin Homology Domain

Overview

Journal Mol Biol Cell

Specialties Cell Biology
Molecular Biology

Date 2006 Sep 15

PMID 16971510

Citations 90

Authors

David E Hokanson

Joseph M Laakso

Tianming Lin

David Sept

E Michael Ostap

Affiliations

Soon will be listed here.

Abstract

Myo1c is a member of the myosin superfamily that binds phosphatidylinositol-4,5-bisphosphate (PIP(2)), links the actin cytoskeleton to cellular membranes and plays roles in mechano-signal transduction and membrane trafficking. We located and characterized two distinct membrane binding sites within the regulatory and tail domains of this myosin. By sequence, secondary structure, and ab initio computational analyses, we identified a phosphoinositide binding site in the tail to be a putative pleckstrin homology (PH) domain. Point mutations of residues known to be essential for polyphosphoinositide binding in previously characterized PH domains inhibit myo1c binding to PIP(2) in vitro, disrupt in vivo membrane binding, and disrupt cellular localization. The extended sequence of this binding site is conserved within other myosin-I isoforms, suggesting they contain this putative PH domain. We also characterized a previously identified membrane binding site within the IQ motifs in the regulatory domain. This region is not phosphoinositide specific, but it binds anionic phospholipids in a calcium-dependent manner. However, this site is not essential for in vivo membrane binding.

Citing Articles

High-resolution structures of Myosin-IC reveal a unique actin-binding orientation, ADP release pathway, and power stroke trajectory.

Chavali S, Carman P, Shuman H, Ostap E, Sindelar C Proc Natl Acad Sci U S A. 2025; 122(9):e2415457122.

PMID: 40014570 PMC: 11892617. DOI: 10.1073/pnas.2415457122.

High resolution structures of Myosin-IC reveal a unique actin-binding orientation, ADP release pathway, and power stroke trajectory.

Chavali S, Carman P, Shuman H, Ostap E, Sindelar C bioRxiv. 2025; .

PMID: 39829824 PMC: 11741418. DOI: 10.1101/2025.01.10.632429.

Myosin-I synergizes with Arp2/3 complex to enhance the pushing forces of branched actin networks.

Xu M, Rutkowski D, Rebowski G, Boczkowska M, Pollard L, Dominguez R Sci Adv. 2024; 10(37):eado5788.

PMID: 39270022 PMC: 11397503. DOI: 10.1126/sciadv.ado5788.

Myo1c drives actin-dependent VWF expulsion from EC WPBs.

Rusu L, Minshall R Blood Adv. 2024; 8(17):4711-4713.

PMID: 39254967 PMC: 11413664. DOI: 10.1182/bloodadvances.2024013476.

Myosin-1C augments endothelial secretion of von Willebrand factor by linking contractile actomyosin machinery to the plasma membrane.

El-Mansi S, Mitchell T, Mobayen G, McKinnon T, Miklavc P, Frick M Blood Adv. 2024; 8(17):4714-4726.

PMID: 38669344 PMC: 11413703. DOI: 10.1182/bloodadvances.2024012590.

References

Kelley L, MacCallum R, STERNBERG M . Enhanced genome annotation using structural profiles in the program 3D-PSSM. J Mol Biol. 2000; 299(2):499-520. DOI: 10.1006/jmbi.2000.3741. View

Huang S, Lifshitz L, Patki-Kamath V, Tuft R, Fogarty K, Czech M . Phosphatidylinositol-4,5-bisphosphate-rich plasma membrane patches organize active zones of endocytosis and ruffling in cultured adipocytes. Mol Cell Biol. 2004; 24(20):9102-23. PMC: 517906. DOI: 10.1128/MCB.24.20.9102-9123.2004. View

Berg J, Powell B, Cheney R . A millennial myosin census. Mol Biol Cell. 2001; 12(4):780-94. PMC: 32266. DOI: 10.1091/mbc.12.4.780. View

Jung G, Remmert K, Wu X, Volosky J, Hammer 3rd J . The Dictyostelium CARMIL protein links capping protein and the Arp2/3 complex to type I myosins through their SH3 domains. J Cell Biol. 2001; 153(7):1479-97. PMC: 2150732. DOI: 10.1083/jcb.153.7.1479. View

Lemmon M, Ferguson K . Molecular determinants in pleckstrin homology domains that allow specific recognition of phosphoinositides. Biochem Soc Trans. 2001; 29(Pt 4):377-84. DOI: 10.1042/bst0290377. View

Tang N, Ostap E . Motor domain-dependent localization of myo1b (myr-1). Curr Biol. 2001; 11(14):1131-5. DOI: 10.1016/s0960-9822(01)00320-7. View

Axelrod D . Total internal reflection fluorescence microscopy in cell biology. Traffic. 2001; 2(11):764-74. DOI: 10.1034/j.1600-0854.2001.21104.x. View

Bonneau R, Strauss C, Rohl C, Chivian D, Bradley P, Malmstrom L . De novo prediction of three-dimensional structures for major protein families. J Mol Biol. 2002; 322(1):65-78. DOI: 10.1016/s0022-2836(02)00698-8. View

Tang N, Lin T, Ostap E . Dynamics of myo1c (myosin-ibeta ) lipid binding and dissociation. J Biol Chem. 2002; 277(45):42763-8. DOI: 10.1074/jbc.M206388200. View

10.

Hirono M, Denis C, Richardson G, Gillespie P . Hair cells require phosphatidylinositol 4,5-bisphosphate for mechanical transduction and adaptation. Neuron. 2004; 44(2):309-20. DOI: 10.1016/j.neuron.2004.09.020. View

11.

Komander D, Fairservice A, Deak M, Kular G, Prescott A, Downes C . Structural insights into the regulation of PDK1 by phosphoinositides and inositol phosphates. EMBO J. 2004; 23(20):3918-28. PMC: 524332. DOI: 10.1038/sj.emboj.7600379. View

12.

Putkey J, Slaughter G, Means A . Bacterial expression and characterization of proteins derived from the chicken calmodulin cDNA and a calmodulin processed gene. J Biol Chem. 1985; 260(8):4704-12. View

13.

Adams R, Pollard T . Binding of myosin I to membrane lipids. Nature. 1989; 340(6234):565-8. DOI: 10.1038/340565a0. View

14.

Miyata H, Bowers B, Korn E . Plasma membrane association of Acanthamoeba myosin I. J Cell Biol. 1989; 109(4 Pt 1):1519-28. PMC: 2115813. DOI: 10.1083/jcb.109.4.1519. View

15.

Hayden S, Wolenski J, Mooseker M . Binding of brush border myosin I to phospholipid vesicles. J Cell Biol. 1990; 111(2):443-51. PMC: 2116197. DOI: 10.1083/jcb.111.2.443. View

16.

COLLINS J . Phosphorylation of brush border myosin I by protein kinase C is regulated by Ca(2+)-stimulated binding of myosin I to phosphatidylserine concerted with calmodulin dissociation. J Biol Chem. 1992; 267(5):3445-54. View

17.

COLLINS J . Calcium regulation of myosin I--a motor for membrane movement. Adv Exp Med Biol. 1992; 321:159-63. DOI: 10.1007/978-1-4615-3448-8_18. View

18.

Peitzsch R, McLaughlin S . Binding of acylated peptides and fatty acids to phospholipid vesicles: pertinence to myristoylated proteins. Biochemistry. 1993; 32(39):10436-43. DOI: 10.1021/bi00090a020. View

19.

Stoffler H, Ruppert C, Reinhard J, Bahler M . A novel mammalian myosin I from rat with an SH3 domain localizes to Con A-inducible, F-actin-rich structures at cell-cell contacts. J Cell Biol. 1995; 129(3):819-30. PMC: 2120456. DOI: 10.1083/jcb.129.3.819. View

20.

Lemmon M, Ferguson K, OBrien R, SIGLER P, Schlessinger J . Specific and high-affinity binding of inositol phosphates to an isolated pleckstrin homology domain. Proc Natl Acad Sci U S A. 1995; 92(23):10472-6. PMC: 40633. DOI: 10.1073/pnas.92.23.10472. View