TY - JOUR
T1 - From Snails to Sciatic Nerve
T2 - Retrograde Injury Signaling from Axon to Soma in Lesioned Neurons
AU - Perlson, Eran
AU - Hanz, Shlomit
AU - Medzihradszky, Katalin F.
AU - Burlingame, Alma L.
AU - Fainzilber, Mike
PY - 2004/2/5
Y1 - 2004/2/5
N2 - The cell body of a lesioned neuron must receive accurate and timely information on the site and extent of axonal damage, in order to mount an appropriate response. Specific mechanisms must therefore exist to transmit such information along the length of the axon from the lesion site to the cell body. Three distinct types of signals have been postulated to underlie this process, starting with injury-induced discharge of axon potentials, and continuing with two distinct types of retrogradely transported macromolecular signals. The latter include, on the one hand, an interruption of the normal supply of retrogradely transported trophic factors from the target; and on the other hand activated proteins emanating from the injury site. These activated proteins are termed "positive injury signals", and are thought to be endogenous axoplasmic proteins that undergo post-translational modifications at the lesion site upon axotomy, which then target them to the retrograde transport system for trafficking to the cell body. Here, we summarize the work to date supporting the positive retrograde injury signal hypothesis, and provide some new and emerging proteomic data on the system. We propose that the retrograde positive injury signals form part of a complex that is assembled by a combination of different processes, including post-translational modifications such as phosphorylation, regulated and transient proteolysis, and local axonal protein synthesis.
AB - The cell body of a lesioned neuron must receive accurate and timely information on the site and extent of axonal damage, in order to mount an appropriate response. Specific mechanisms must therefore exist to transmit such information along the length of the axon from the lesion site to the cell body. Three distinct types of signals have been postulated to underlie this process, starting with injury-induced discharge of axon potentials, and continuing with two distinct types of retrogradely transported macromolecular signals. The latter include, on the one hand, an interruption of the normal supply of retrogradely transported trophic factors from the target; and on the other hand activated proteins emanating from the injury site. These activated proteins are termed "positive injury signals", and are thought to be endogenous axoplasmic proteins that undergo post-translational modifications at the lesion site upon axotomy, which then target them to the retrograde transport system for trafficking to the cell body. Here, we summarize the work to date supporting the positive retrograde injury signal hypothesis, and provide some new and emerging proteomic data on the system. We propose that the retrograde positive injury signals form part of a complex that is assembled by a combination of different processes, including post-translational modifications such as phosphorylation, regulated and transient proteolysis, and local axonal protein synthesis.
KW - Axon
KW - Nerve injury
KW - Regeneration
KW - Retrograde transport
UR - http://www.scopus.com/inward/record.url?scp=0842333841&partnerID=8YFLogxK
U2 - 10.1002/neu.10316
DO - 10.1002/neu.10316
M3 - סקירה
C2 - 14704959
AN - SCOPUS:0842333841
VL - 58
SP - 287
EP - 294
JO - Developmental Neurobiology
JF - Developmental Neurobiology
SN - 1932-8451
IS - 2
ER -