Abstract
Protein factors derived from skeletal muscle separately promote neurite elongation and acetylcholine synthesis in cultured rat ventral spinal neurons. Morphologic factor activity (neurite-inducing activity) is specifically found in rat skeletal muscle and cord neuron extracts, decreases with the postnatal age of the rats from which muscle extract is prepared, and increases in rat hindlimb muscle after 5 d of denervation. Cholinergic factor activity (acetylcholine synthesis- stimulating activity) is found in extracts of rat cerebral cortex and cardiac muscle in addition to spinal cord and skeletal muscle, increases with animal age, and decreases following 5 d of denervation. Biochemically, the factors responsible for these activities differ in their lability to denaturing conditions, apparent molecular weights, isoelectric points, and lectin-binding specificities. Under reducing conditions, morphologic activity is isolated in a single acidic glycoprotein with an Mr of 35,000, while acetylcholine synthesis- stimulating activity is found in multiple species of different molecular weights. Thus, acetylcholine synthesis-promoting activities and neurite growth-promoting activity appear to reside in different molecules. Significant purification of several of these factors has been achieved.
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- Baenziger J. U., Fiete D. Structural determinants of concanavalin A specificity for oligosaccharides. J Biol Chem. 1979 Apr 10;254(7):2400–2407. [PubMed] [Google Scholar]
- Barbin G., Manthorpe M., Varon S. Purification of the chick eye ciliary neuronotrophic factor. J Neurochem. 1984 Nov;43(5):1468–1478. doi: 10.1111/j.1471-4159.1984.tb05410.x. [DOI] [PubMed] [Google Scholar]
- Bennett M. R., Lai K., Nurcombe V. Identification of embryonic motoneurons in vitro: their survival is dependent on skeletal muscle. Brain Res. 1980 May 26;190(2):537–542. doi: 10.1016/0006-8993(80)90295-4. [DOI] [PubMed] [Google Scholar]
- Benoit P., Changeux J. P. Consequences of tenotomy on the evolution of multiinnervation in developing rat soleus muscle. Brain Res. 1975 Dec 5;99(2):354–358. doi: 10.1016/0006-8993(75)90036-0. [DOI] [PubMed] [Google Scholar]
- Brown M. C., Holland R. L., Ironton R. Nodal and terminal sprouting from motor nerves in fast and slow muscles of the mouse. J Physiol. 1980 Sep;306:493–510. doi: 10.1113/jphysiol.1980.sp013410. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Burt A. M. Choline acetyltransferase and acetylcholinesterase in the developing rat spinal cord. Exp Neurol. 1975 Apr;47(1):173–180. doi: 10.1016/0014-4886(75)90245-9. [DOI] [PubMed] [Google Scholar]
- Calof A. L., Reichardt L. F. Motoneurons purified by cell sorting respond to two distinct activities in myotube-conditioned medium. Dev Biol. 1984 Nov;106(1):194–210. doi: 10.1016/0012-1606(84)90075-7. [DOI] [PubMed] [Google Scholar]
- Carbonetto S., Muller K. J. Nerve fiber growth and the cellular response to axotomy. Curr Top Dev Biol. 1982;17(Pt 3):33–76. doi: 10.1016/s0070-2153(08)60518-9. [DOI] [PubMed] [Google Scholar]
- Collins F., Dawson A. Conditioned medium increases the rate of neurite elongation: separation of this activity from the substratum-bound inducer of neurite outgrowth. J Neurosci. 1982 Aug;2(8):1005–1010. doi: 10.1523/JNEUROSCI.02-08-01005.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Collins F. Induction of neurite outgrowth by a conditioned-medium factor bound to the culture substratum. Proc Natl Acad Sci U S A. 1978 Oct;75(10):5210–5213. doi: 10.1073/pnas.75.10.5210. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dribin L. B., Barrett J. N. Characterization of neuritic outgrowth-promoting activity of conditioned medium on spinal cord explants. Brain Res. 1982 Aug;256(4):435–441. doi: 10.1016/0165-3806(82)90187-0. [DOI] [PubMed] [Google Scholar]
- Dribin L. B., Barrett J. N. Conditioned medium enhances neuritic outgrowth from rat spinal cord explants. Dev Biol. 1980 Jan;74(1):184–195. doi: 10.1016/0012-1606(80)90060-3. [DOI] [PubMed] [Google Scholar]
- ELLMAN G. L., COURTNEY K. D., ANDRES V., Jr, FEATHER-STONE R. M. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol. 1961 Jul;7:88–95. doi: 10.1016/0006-2952(61)90145-9. [DOI] [PubMed] [Google Scholar]
- Ebendal T., Belew M., Jacobson C. O., Porath J. Neurite outgrowth elicited by embryonic chick heart: partial purification of the active factor. Neurosci Lett. 1979 Sep;14(1):91–95. doi: 10.1016/0304-3940(79)95350-3. [DOI] [PubMed] [Google Scholar]
- Fonnum F. Radiochemical micro assays for the determination of choline acetyltransferase and acetylcholinesterase activities. Biochem J. 1969 Nov;115(3):465–472. doi: 10.1042/bj1150465. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Godfrey E. W., Schrier B. K., Nelson P. G. Source and target cell specificities of a conditioned medium factor that increases choline acetyltransferase activity in cultured spinal cord cells. Dev Biol. 1980 Jun 15;77(2):403–418. doi: 10.1016/0012-1606(80)90484-4. [DOI] [PubMed] [Google Scholar]
- Gray A., Dull T. J., Ullrich A. Nucleotide sequence of epidermal growth factor cDNA predicts a 128,000-molecular weight protein precursor. Nature. 1983 Jun 23;303(5919):722–725. doi: 10.1038/303722a0. [DOI] [PubMed] [Google Scholar]
- Gurney M. E. Suppression of sprouting at the neuromuscular junction by immune sera. Nature. 1984 Feb 9;307(5951):546–548. doi: 10.1038/307546a0. [DOI] [PubMed] [Google Scholar]
- Hamburger V. Cell death in the development of the lateral motor column of the chick embryo. J Comp Neurol. 1975 Apr 15;160(4):535–546. doi: 10.1002/cne.901600408. [DOI] [PubMed] [Google Scholar]
- Heiwall P. O., Dahlström A., Larsson P. A., Böj S. The intra-axonal transport of acetylcholine and cholinergic enzymes in rat sciatic nerve during regeneration after various types of axonal trauma. J Neurobiol. 1979 Mar;10(2):119–136. doi: 10.1002/neu.480100203. [DOI] [PubMed] [Google Scholar]
- Henderson C. E., Huchet M., Changeux J. P. Neurite outgrowth from embryonic chicken spinal neurons is promoted by media conditioned by muscle cells. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2625–2629. doi: 10.1073/pnas.78.4.2625. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hinegardner R. T. An improved fluorometric assay for DNA. Anal Biochem. 1971 Jan;39(1):197–201. doi: 10.1016/0003-2697(71)90476-3. [DOI] [PubMed] [Google Scholar]
- Johnson D. A., Pilar G. The release of acetylcholine from post-ganglionic cell bodies in response to depolarization. J Physiol. 1980 Feb;299:605–619. doi: 10.1113/jphysiol.1980.sp013144. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kaufman L. M., Barrett J. N. Serum factor supporting long-term survival of rat central neurons in culture. Science. 1983 Jun 24;220(4604):1394–1396. doi: 10.1126/science.6857258. [DOI] [PubMed] [Google Scholar]
- Kaufman L. M., Barry S. R., Barrett J. N. Characterization of tissue-derived macromolecules affecting transmitter synthesis in rat spinal cord neurons. J Neurosci. 1985 Jan;5(1):160–166. doi: 10.1523/JNEUROSCI.05-01-00160.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kligman D. Isolation of a protein from bovine brain which promotes neurite extension from chick embryo cerebral cortex neurons in defined medium. Brain Res. 1982 Oct 28;250(1):93–100. doi: 10.1016/0006-8993(82)90955-6. [DOI] [PubMed] [Google Scholar]
- Kornfeld K., Reitman M. L., Kornfeld R. The carbohydrate-binding specificity of pea and lentil lectins. Fucose is an important determinant. J Biol Chem. 1981 Jul 10;256(13):6633–6640. [PubMed] [Google Scholar]
- LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
- Lance-Jones C. Motoneuron cell death in the developing lumbar spinal cord of the mouse. Brain Res. 1982 Aug;256(4):473–479. doi: 10.1016/0165-3806(82)90192-4. [DOI] [PubMed] [Google Scholar]
- Lander A. D., Fujii D. K., Reichardt L. F. Laminin is associated with the "neurite outgrowth-promoting factors" found in conditioned media. Proc Natl Acad Sci U S A. 1985 Apr;82(7):2183–2187. doi: 10.1073/pnas.82.7.2183. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Longo F. M., Manthorpe M., Varon S. Spinal cord neuronotrophic factors (SCNTFs): I. Bioassay of schwannoma and other conditioned media. Brain Res. 1982 Feb;255(2):277–294. doi: 10.1016/0165-3806(82)90027-x. [DOI] [PubMed] [Google Scholar]
- Matrisian L. M., Pathak M., Magun B. E. Identification of an epidermal growth factor-related transforming growth factor from rat fetuses. Biochem Biophys Res Commun. 1982 Aug;107(3):761–769. doi: 10.1016/0006-291x(82)90589-7. [DOI] [PubMed] [Google Scholar]
- Mickey D. D., McMillan P. N., Appel S. H., Day E. D. The specificity and cross-reactivity of antisynaptosome antibodies as determined by sequential adsorption analysis. J Immunol. 1971 Dec;107(6):1599–1610. [PubMed] [Google Scholar]
- Niall H. D. The evolution of peptide hormones. Annu Rev Physiol. 1982;44:615–624. doi: 10.1146/annurev.ph.44.030182.003151. [DOI] [PubMed] [Google Scholar]
- Nishi R., Berg D. K. Two components from eye tissue that differentially stimulate the growth and development of ciliary ganglion neurons in cell culture. J Neurosci. 1981 May;1(5):505–513. doi: 10.1523/JNEUROSCI.01-05-00505.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nurcombe V., Hill M. A., Eagleson K. L., Bennett M. R. Motor neuron survival and neuritic extension from spinal cord explants induced by factors released from denervated muscle. Brain Res. 1984 Jan 16;291(1):19–28. doi: 10.1016/0006-8993(84)90646-2. [DOI] [PubMed] [Google Scholar]
- O'Brien R. A., Ostberg A. J., Vrbová G. Observations on the elimination of polyneuronal innervation in developing mammalian skeletal muscle. J Physiol. 1978 Sep;282:571–582. doi: 10.1113/jphysiol.1978.sp012482. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Oppenheim R. W., Majors-Willard C. Neuronal cell death in the brachial spinal cord of the chick is unrelated to the loss of polyneuronal innervation in wing muscle. Brain Res. 1978 Oct 6;154(1):148–152. doi: 10.1016/0006-8993(78)91062-4. [DOI] [PubMed] [Google Scholar]
- Pestronk A., Drachman D. B., Stanley E. F., Price D. L., Griffin J. W. Cholinergic transmission regulates extrajunctional acetylcholine receptors. Exp Neurol. 1980 Dec;70(3):690–696. doi: 10.1016/0014-4886(80)90193-4. [DOI] [PubMed] [Google Scholar]
- Pilar G., Tuttle J., Vaca K. Functional maturation of motor nerve terminals in the avian iris: ultrastructure, transmitter metabolism and synaptic reliability. J Physiol. 1981 Dec;321:175–193. doi: 10.1113/jphysiol.1981.sp013978. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pittman R. H., Oppenheim R. W. Neuromuscular blockade increases motoneurone survival during normal cell death in the chick embryo. Nature. 1978 Jan 26;271(5643):364–366. doi: 10.1038/271364a0. [DOI] [PubMed] [Google Scholar]
- Purves D. Neuronal competition. Nature. 1980 Oct 16;287(5783):585–586. doi: 10.1038/287585a0. [DOI] [PubMed] [Google Scholar]
- Sanes J. R. More nerve growth factors? Nature. 1984 Feb 9;307(5951):500–500. doi: 10.1038/307500a0. [DOI] [PubMed] [Google Scholar]
- Sarthy P. V., Rayborn M. E., Hollyfield J. G., Lam D. M. The emergence, localization, and maturation of neurotransmitter systems during development of the retina in Xenopus laevis. III. Dopamine. J Comp Neurol. 1981 Feb 1;195(4):595–602. doi: 10.1002/cne.901950405. [DOI] [PubMed] [Google Scholar]
- Smith R. G., Appel S. H. Extracts of skeletal muscle increase neurite outgrowth and cholinergic activity of fetal rat spinal motor neurons. Science. 1983 Mar 4;219(4588):1079–1081. doi: 10.1126/science.6823568. [DOI] [PubMed] [Google Scholar]
- Tanaka H., Obata K. Survival and neurite growth of chick embryo spinal cord cells in serum-free culture. Brain Res. 1982 Jul;256(3):313–321. doi: 10.1016/0165-3806(82)90143-2. [DOI] [PubMed] [Google Scholar]
- Thoenen H., Barde Y. A. Physiology of nerve growth factor. Physiol Rev. 1980 Oct;60(4):1284–1335. doi: 10.1152/physrev.1980.60.4.1284. [DOI] [PubMed] [Google Scholar]
- Udenfriend S., Stein S., Böhlen P., Dairman W., Leimgruber W., Weigele M. Fluorescamine: a reagent for assay of amino acids, peptides, proteins, and primary amines in the picomole range. Science. 1972 Nov 24;178(4063):871–872. doi: 10.1126/science.178.4063.871. [DOI] [PubMed] [Google Scholar]
- Waterfield M. D., Scrace G. T., Whittle N., Stroobant P., Johnsson A., Wasteson A., Westermark B., Heldin C. H., Huang J. S., Deuel T. F. Platelet-derived growth factor is structurally related to the putative transforming protein p28sis of simian sarcoma virus. Nature. 1983 Jul 7;304(5921):35–39. doi: 10.1038/304035a0. [DOI] [PubMed] [Google Scholar]
- Watson W. E. Cellular responses to axotomy and to related procedures. Br Med Bull. 1974 May;30(2):112–115. doi: 10.1093/oxfordjournals.bmb.a071179. [DOI] [PubMed] [Google Scholar]
- Weber M. J. A diffusible factor responsible for the determination of cholinergic functions in cultured sympathetic neurons. Partial purification and characterization. J Biol Chem. 1981 Apr 10;256(7):3447–3453. [PubMed] [Google Scholar]