Design of active transport must be highly intricate: a possible role of myosin and Ena/VASP for G-actin transport in filopodia.
Recent modeling of filopodia--the actin-based cell organelles employed for sensing and motility--reveals that one of the key limiting factors of filopodial length is diffusional transport of G-actin monomers to the polymerizing barbed ends. We have explored the possibility of active transport of G-actin by myosin motors, which would be an expected biological response to overcome the limitation of a diffusion-based process. We found that in a straightforward implementation of active transport the increase in length was unimpressive, < or = 30%, due to sequestering of G-actin by freely diffusing motors. However, artificially removing motor sequestration reactions led to approximately threefold increases in filopodial length, with the transport being mainly limited by the motors failing to detach from the filaments near the tip, clogging the cooperative conveyer belt dynamics. Making motors sterically transparent led to a qualitative change of the dynamics to a different regime of steady growth without a stationary length. Having identified sequestration and clogging as ubiquitous constraints to motor-driven transport, we devised and tested a speculative means to sidestep these limitations in filopodia by employing cross-linking and putative scaffolding roles of Ena/VASP proteins. We conclude that a naïve design of molecular-motor-based active transport would almost always be inefficient--an intricately organized kinetic scheme, with finely tuned rate constants, is required to achieve high-flux transport.
Zhuravlev
Pavel I
PI
Department of Chemistry, University of North Carolina, Chapel Hill, North Carolina, USA.
Der
Bryan S
BS
Papoian
Garegin A
GA
D000199:Actins / Q000378:metabolism*; D000818:Animals; D001693:Biological Transport, Active; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D003198:Computer Simulation; D004058:Diffusion; D008840:Microfilament Proteins / Q000378:metabolism*; D008954:Models, Biological; D009218:Myosins / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D021381:Protein Transport; D011554:Pseudopodia / Q000378:metabolism*; D000098662:Vasodilator-Stimulated Phosphoprotein
D000199:Actins; D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; D010750:Phosphoproteins; D000098662:Vasodilator-Stimulated Phosphoprotein; D009218:Myosins
Science. 2001 May 25;292(5521):1502-6
11379633
Curr Biol. 2007 Apr 3;17(7):R244-7
17407753
Biochem Biophys Res Commun. 2004 Jun 18;319(1):214-20
15158464
Nat Cell Biol. 2002 Nov;4(11):E251-3
12415279
Science. 2003 Apr 4;300(5616):142-5
12677069
Curr Biol. 2009 Jun 9;19(11):967-73
19398338
Nat Cell Biol. 2004 Jun;6(6):523-31
15156152
Cancer Cell. 2006 Apr;9(4):261-72
16616332
Neuron. 2003 Oct 9;40(2):209-27
14556705
Phys Rev Lett. 2006 Jul 7;97(1):018101
16907410
Biophys J. 2008 May 15;94(10):3839-52
18234810
Biophys J. 2001 Dec;81(6):3116-36
11720979
J Biol Chem. 2005 Oct 14;280(41):34702-8
16030012
Nat Neurosci. 2001 Aug;4(8):787-93
11477424
Biophys J. 2005 Aug;89(2):782-95
15879474
Mol Biol Cell. 2001 Apr;12(4):780-94
11294886
Curr Opin Cell Biol. 2006 Feb;18(1):18-25
16337369
Proc Natl Acad Sci U S A. 2005 Dec 27;102(52):18926-31
16361441
Phys Rev Lett. 2004 Dec 17;93(25):256001
15697914
Biophys J. 2007 Aug 15;93(4):1124-33
17526588
Proc Natl Acad Sci U S A. 2007 Nov 27;104(48):18958-63
18025473
Annu Rev Biophys Biomol Struct. 2000;29:545-76
10940259
PLoS One. 2009;4(3):e4810
19277198
J Cell Sci. 2003 Mar 15;116(Pt 6):1087-94
12584251
Proc Natl Acad Sci U S A. 2006 May 16;103(20):7694-9
16675552
Int J Biochem Cell Biol. 2002 Jul;34(7):726-30
11950590
Cell. 2005 Jul 29;122(2):169-82
16051143
Nature. 2004 Apr 1;428(6982):574-8
15058306
Biophys J. 2006 Jan 1;90(1):65-76
16214866
J Neurosci Res. 1985;13(1-2):149-62
3973930
J Cell Biol. 1986 Dec;103(6 Pt 2):2747-54
3793756
J Cell Sci. 2005 May 15;118(Pt 10):2225-37
15855234
Dev Biol. 2002 Aug 15;248(2):307-18
12167406
Genetics. 2004 May;167(1):523-30
15166174
Cell. 2003 Feb 21;112(4):453-65
12600310
FEBS Lett. 1999 May 14;451(1):68-74
10356985
J Struct Biol. 2006 Aug;155(2):195-201
16684607
Proc Natl Acad Sci U S A. 2009 Jul 14;106(28):11570-5
19556544
J Cell Biol. 2000 Jan 10;148(1):127-36
10629223
Phys Rev Lett. 2007 Jun 1;98(22):228301
17677882
Biophys J. 2006 Apr 15;90(8):2673-85
16443647
Mol Biol Cell. 2007 Jul;18(7):2579-91
17475772
Nat Cell Biol. 2009 Apr;11(4):443-50
19287378
Proc Natl Acad Sci U S A. 2008 Jul 15;105(28):9616-20
18599451
Curr Biol. 2004 Apr 20;14(8):697-703
15084285
Exp Cell Res. 1961 Jun;24:64-79
13709960
Nat Cell Biol. 2002 Mar;4(3):246-50
11854753
Biophys J. 2008 Dec 15;95(12):5706-18
18936243
Biophys J. 2008 Aug;95(4):1627-38
18502800
Biochemistry. 1992 Jul 14;31(27):6179-85
1627561
Proc Natl Acad Sci U S A. 2006 Aug 15;103(33):12411-6
16894163
Cell Motil Cytoskeleton. 2002 Jan;51(1):27-38
11810694
J Chem Phys. 2006 Sep 28;125(12):124106
17014165
J Cell Biol. 2005 Aug 15;170(4):619-26
16103229
Annu Rev Cell Dev Biol. 2003;19:541-64
14570581
Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2374-9
12606710
Cell Motil Cytoskeleton. 1992;22(3):160-9
1423662
J Cell Sci. 2000 Oct;113 Pt 19:3439-51
10984435
Trans Am Microsc Soc. 1976 Apr;95(2):165-73
944962
Biochim Biophys Acta. 2010 Feb;1803(2):191-200
19171166
J Biol Chem. 2005 Aug 5;280(31):28653-62
15939738
Development. 1995 Aug;121(8):2501-11
7671814
J Chem Phys. 2006 Oct 21;125(15):154901
17059287
Neuron. 1996 Apr;16(4):769-82
8607995
J Biol Chem. 1986 Sep 25;261(27):12754-8
3745211