Lipoprotein uptake by neuronal growth cones in vitro.

Macrophages that rapidly enter injured peripheral nerve synthesize and secrete large quantities of apolipoprotein E. This protein may be involved in the redistribution of lipid, including cholesterol released during degeneration, to the regenerating axons. To test this postulate, apolipoprotein E-associated lipid particles released from segments of injured rat sciatic nerve and apolipoprotein E-containing lipoproteins from plasma were used to determine whether sprouting neurites, specifically their growth cones, possessed lipoprotein receptors. Pheochromocytoma (PC12) cells, which can be stimulated to produce neurites in vitro, were used as a model system. Apolipoprotein E-containing lipid particles and lipoproteins, which had been labeled with fluorescent dye, were internalized by the neurites and their growth cones; the unmetabolized dye appeared to be localized to the lysosomes. The rapid rate of accumulation in the growth cones precludes the possibility of orthograde transport of the fluorescent particles from the PC12 cell bodies. Thus, receptor-mediated lipoprotein uptake is performed by the apolipoprotein B,E(LDL) (low density lipoprotein) receptors, and in the regenerating peripheral nerve apolipoprotein E may deliver lipids to the neurites and their growth cones for membrane biosynthesis.

[1]  R. E. Pitas,et al.  Apolipoprotein E in nerve injury and repair. , 1987, Progress in brain research.

[2]  M. Brown,et al.  A receptor-mediated pathway for cholesterol homeostasis. , 1986, Science.

[3]  J. Freeman,et al.  Nerve injury stimulates the secretion of apolipoprotein E by nonneuronal cells. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[4]  E. Shooter,et al.  Expression of apolipoprotein E during nerve degeneration and regeneration. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[5]  E. Shooter,et al.  Expression of specific sheath cell proteins during peripheral nerve growth and regeneration in mammals , 1986, The Journal of cell biology.

[6]  E. Shooter,et al.  A specific 37,000-dalton protein that accumulates in regenerating but not in nonregenerating mammalian nerves. , 1985, Science.

[7]  R. Mahley,et al.  Uptake of chemically modified low density lipoproteins in vivo is mediated by specific endothelial cells , 1985, The Journal of cell biology.

[8]  R. Mahley,et al.  Plasma lipoproteins: apolipoprotein structure and function. , 1984, Journal of lipid research.

[9]  J. Skene.  Growth-associated proteins and the curious dichotomies of nerve regeneration , 1984, Cell.

[10]  A. Oaklander,et al.  Reactive glial protein synthesis and early disappearance of saxitoxin binding in degenerating rat optic nerve , 1983, Brain Research.

[11]  E. Shooter,et al.  Denervated sheath cells secrete a new protein after nerve injury. , 1983, Proceedings of the National Academy of Sciences of the United States of America.

[12]  R. Mahley,et al.  Lipoprotein receptors and cholesterol homeostasis. , 1983, Biochimica et biophysica acta.

[13]  R. Mahley,et al.  Foam Cells in Explants of Atherosclerotic Rabbit Aortas Have Receptors for β‐Very Low Density Low Density Lipoproteins and Modified Low Density Lipoproteins , 1983, Arteriosclerosis.

[14]  S. Landis,et al.  Neuronal growth cones. , 1983, Annual review of physiology.

[15]  T. Ebendal,et al.  Nerve growth activities in rat peripheral nerve , 1982, Brain Research.

[16]  A. Aguayo,et al.  Extensive elongation of axons from rat brain into peripheral nerve grafts , 1982, Nature.

[17]  J. Weinstein,et al.  Acetoacetylated Lipoproteins Used to Distinguish Fibroblasts from Macrophages In Vitro by Fluorescence Microscopy , 1981, Arteriosclerosis.

[18]  B. Grafstein,et al.  Intracellular transport in neurons. , 1980, Physiological reviews.

[19]  C. Raine,et al.  Reinnervation of peripheral nerve segments implanted into the rat central nervous system , 1980, Brain Research.

[20]  R. Mahley,et al.  Cell surface receptor binding of phospholipid . protein complexes containing different ratios of receptor-active and -inactive E apoprotein. , 1980, The Journal of biological chemistry.

[21]  A. Aguayo,et al.  Axons from CNS neurones regenerate into PNS grafts , 1980, Nature.

[22]  R. Mahley,et al.  Subfractionation of human high density lipoproteins by heparin-Sepharose affinity chromatography. , 1980, Journal of lipid research.

[23]  N. K. Wessells,et al.  chapter 5 Regulation of the Elongating Nerve Fiber , 1980 .

[24]  H. Towbin,et al.  Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[25]  M. Brown,et al.  Receptor-mediated endocytosis: insights from the lipoprotein receptor system. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[26]  R. Mahley,et al.  Binding of arginine-rich (E) apoprotein after recombination with phospholipid vesicles to the low density lipoprotein receptors of fibroblasts. , 1979, The Journal of biological chemistry.

[27]  K. Pfenninger,et al.  Properties and dynamics of plasmalemmal glycoconjugates in growing neurites. , 1979, Progress in brain research.

[28]  LA Greene,et al.  Nerve growth factor prevents the death and stimulates the neuronal differentiation of clonal PC12 pheochromocytoma cells in serum-free medium , 1978, The Journal of cell biology.

[29]  M. Willard,et al.  Subcellular fractionation of intra-axonally transport polypeptides in the rabbit visual system. , 1978, Proceedings of the National Academy of Sciences of the United States of America.

[30]  M. Bunge.  Initial endocytosis of peroxidase or ferritin by growth cones of cultured nerve cells , 1977, Journal of neurocytology.

[31]  R. Behin,et al.  Quantitative release of live microorganisms from infected macrophages by sodium dodecyl sulphate. , 1973, Nature: New biology.

[32]  D. Bray,et al.  Model for Membrane Movements in the Neural Growth Cone , 1973, Nature.

[33]  E. Hedley‐Whyte,et al.  FINE STRUCTURAL LOCALIZATION OF CHOLESTEROL-1,2-3H IN DEGENERATING AND REGENERATING MOUSE SCIATIC NERVE , 1972, The Journal of cell biology.

[34]  N. K. Wessells,et al.  ULTRASTRUCTURE AND FUNCTION OF GROWTH CONES AND AXONS OF CULTURED NERVE CELLS , 1971, The Journal of cell biology.

[35]  U. K. Laemmli,et al.  Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4 , 1970, Nature.

[36]  E. Hedley‐Whyte,et al.  Reutilization of cholesterol-1,2-H3 in the regeneration of peripheral nerve. An autoradiographic study. , 1970, Laboratory investigation; a journal of technical methods and pathology.

[37]  L. Guth.  Regeneration in the mammalian peripheral nervous system. , 1956, Physiological reviews.