Can molecular motors drive distance measurements in injured neurons?
Injury to nerve axons induces diverse responses in neuronal cell bodies, some of which are influenced by the distance from the site of injury. This suggests that neurons have the capacity to estimate the distance of the injury site from their cell body. Recent work has shown that the molecular motor dynein transports importin-mediated retrograde signaling complexes from axonal lesion sites to cell bodies, raising the question whether dynein-based mechanisms enable axonal distance estimations in injured neurons? We used computer simulations to examine mechanisms that may provide nerve cells with dynein-dependent distance assessment capabilities. A multiple-signals model was postulated based on the time delay between the arrival of two or more signals produced at the site of injury-a rapid signal carried by action potentials or similar mechanisms and slower signals carried by dynein. The time delay between the arrivals of these two types of signals should reflect the distance traversed, and simulations of this model show that it can indeed provide a basis for distance measurements in the context of nerve injuries. The analyses indicate that the suggested mechanism can allow nerve cells to discriminate between distances differing by 10% or more of their total axon length, and suggest that dynein-based retrograde signaling in neurons can be utilized for this purpose over different scales of nerves and organisms. Moreover, such a mechanism might also function in synapse to nucleus signaling in uninjured neurons. This could potentially allow a neuron to dynamically sense the relative lengths of its processes on an ongoing basis, enabling appropriate metabolic output from cell body to processes.
Kam
Naaman
N
Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel.
Pilpel
Yitzhak
Y
Fainzilber
Mike
M
D003198:Computer Simulation; D003627:Data Interpretation, Statistical; D016208:Databases, Factual; D004398:Dyneins / Q000502:physiology*; D008959:Models, Neurological; D009474:Neurons / Q000502:physiology*; D059348:Peripheral Nerve Injuries; D015398:Signal Transduction
D004398:Dyneins
J Theor Biol. 2009 Apr 7;257(3):430-7
19150364
J Comp Neurol. 1984 Dec 20;230(4):497-516
6520248
J Comp Neurol. 1977 Jan 1;171(1):65-81
830672
Mol Syst Biol. 2006;2:61
17102806
Mol Cell Neurosci. 2000 Feb;15(2):170-82
10673325
Exp Neurol. 2008 Feb;209(2):389-98
17610877
J Neurocytol. 1987 Dec;16(6):829-41
3450792
Int Rev Neurobiol. 1971;14:49-124
4948651
Nature. 2004 Feb 12;427(6975):649-52
14961123
J Neurosci. 1998 Oct 1;18(19):7912-29
9742159
Invest Ophthalmol Vis Sci. 2000 Sep;41(10):3165-70
10967079
J Cell Biol. 2008 Jun 16;181(6):1027-39
18559670
J Physiol. 1968 Jun;196(3):655-76
5664236
Prog Neurobiol. 2007 Jan;81(1):1-28
17234322
FASEB J. 2004 Dec;18(15):1934-6
15451889
J Cell Biol. 2000 Mar 6;148(5):945-56
10704445
Neuron. 2006 Oct 19;52(2):293-305
17046692
Nat Cell Biol. 2006 Jun;8(6):562-70
16715075
Brain Res. 1997 Mar 14;751(1):90-5
9098571
PLoS Biol. 2008 Feb;6(2):e34
18303947
J Neurobiol. 2004 Feb 5;58(2):207-16
14704953
Eur J Neurosci. 2003 Oct;18(8):2146-58
14622175
Theor Biol Med Model. 2005 Oct 19;2:43
16236165
Curr Opin Neurobiol. 2008 Jun;18(3):276-83
18655834
J Exp Biol. 2003 Jun;206(Pt 12):2073-82
12756289
Neuron. 2003 Dec 18;40(6):1095-104
14687545
Neuron. 1991 Apr;6(4):635-47
1826603
J Neurobiol. 2004 Feb 5;58(2):287-94
14704959
Neuron. 2004 Dec 16;44(6):997-1009
15603742
Bioessays. 2004 Nov;26(11):1185-94
15499580
Exp Biol Med (Maywood). 2008 Apr;233(4):385-93
18367626
Neuron. 2005 Mar 3;45(5):715-26
15748847
J Math Biol. 2009 Jan;58(1-2):35-55
18283462
Neuron. 2008 Jul 31;59(2):241-52
18667152
J Comp Neurol. 1999 Nov 29;414(4):495-510
10531542
Trends Cell Biol. 2007 Nov;17(11):519-28
18029183
Annu Rev Immunol. 1996;14:233-58
8717514
J Neurochem. 2006 Oct;99(1):13-9
16899067
J Neurosci. 1998 Feb 15;18(4):1318-28
9454841
Brain Res. 1970 Sep 29;23(1):1-21
4919474
Eur J Neurosci. 2003 Aug;18(4):789-802
12925005
Development. 1999 May;126(9):1947-56
10101128
Exp Neurol. 2008 Feb;209(2):313-20
17927983