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The Journal of Neuroscience, November 1, 1999, 19(21):9322-9331
Analysis of the Retrograde Transport of Glial Cell Line-Derived
Neurotrophic Factor (GDNF), Neurturin, and Persephin Suggests That
In Vivo Signaling for the GDNF Family is GFR
Coreceptor-Specific
Melanie L.
Leitner1, 2,
Derek C.
Molliver4,
Patricia A.
Osborne1, 2,
Richard
Vejsada6,
Judy P.
Golden1, 2,
Patricia A.
Lampe1, 2,
Ann C.
Kato5,
Jeffrey
Milbrandt3, and
Eugene M.
Johnson Jr1, 2
Departments of 1 Neurology, 2 Molecular
Biology and Pharmacology, and 3 Pathology and Internal
Medicine, Washington University School of Medicine, St. Louis, Missouri
63110, 4 The Vollum Institute for Advanced Medical
Research, Oregon Health Sciences University, Portland, Oregon 97201, 5 Geneva University Medical School, CH-1211 Geneva 4, Switzerland, and 6 Astra Clinical Research Unit/Central
Europe, Prague, Czech Republic
Neurturin (NRTN) and glial cell line-derived neurotrophic factor
(GDNF) are members of a family of trophic factors with similar actions
in vitro on certain neuronal classes. Retrograde
transport of GDNF and NRTN was compared in peripheral sensory,
sympathetic, and motor neurons to determine whether in
vivo these factors are transported selectively by
different neuronal populations. After sciatic nerve injections, NRTN
was transported by sensory neurons of the dorsal root ganglion (DRG).
Competition studies demonstrated only limited cross-competition between
NRTN and GDNF, indicating selective receptor-mediated transport of
these factors. By using immunohistochemistry, we identified two
populations of NRTN-transporting DRG neurons: a major population of
small, RET-positive, IB4-positive, non-TrkA-expressing neurons that
also show the ability to transport GDNF and a minor population of
calretinin-expressing neurons that fail to transport GDNF. Spinal motor
neurons in the adult showed relatively less ability to transport
NRTN than to transport GDNF, although NRTN prevented the cell death of
neonatal motor neurons in a manner very similar to GDNF (Yan et al.,
1995) and persephin (PSPN) (Milbrandt et al., 1998). Last, NRTN, like
GDNF, was not transported to sympathetic neurons of the adult superior
cervical ganglion (SCG) after injection into the anterior eye chamber. These data reveal a high degree of functional selectivity of GDNF family receptor- (GFR) coreceptor subtypes for NRTN and GDNF in vivo.
Key words:
TrkA; DRG; RET; development; motor neurons; neurotrophic
factors
Copyright © 1999 Society for Neuroscience 0270-6474/99/19219322-10$05.00/0
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