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PMID: 9245793 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Suppression of KIF2 in PC12 cells alters the distribution of a growth cone nonsynaptic membrane receptor and inhibits neurite extension.

The Journal of cell biology ·Vol. 138 ·No. 3 ·1997-08-11 ·Pages 657-69

Morfini G, Quiroga S, Rosa A, Kosik K, Cáceres A

Abstract

In the present study, we present evidence about the cellular functions of KIF2, a kinesin-like superfamily member having a unique structure in that its motor domain is localized at the center of the molecule (Noda Y., Y. Sato-Yoshitake, S. Kondo, M. Nangaku, and N. Hirokawa. 1995. J. Cell Biol. 129:157-167.). Using subcellular fractionation techniques, isopicnic sucrose density centrifugation of microsomal fractions from developing rat cerebral cortex, and immunoisolation with KIF2 antibodies, we have now identified a type of nonsynaptic vesicle that associates with KIF2. This type of organelle lacks synaptic vesicle markers (synapsin, synaptophysin), amyloid precursor protein, GAP-43, or N-cadherin. On the other hand, it contains betagc, which is a novel variant of the beta subunit of the IGF-1 receptor, which is highly enriched in growth cone membranes. Both betagc and KIF2 are upregulated by NGF in PC12 cells and highly concentrated in growth cones of developing neurons. We have also analyzed the consequences of KIF2 suppression by antisense oligonucleotide treatment on nerve cell morphogenesis and the distribution of synaptic and nonsynaptic vesicle markers. KIF2 suppression results in a dramatic accumulation of betagc within the cell body and in its complete disappearance from growth cones; no alterations in the distribution of synapsin, synaptophysin, GAP-43, or amyloid percursor protein are detected in KIF2-suppressed neurons. Instead, all of them remained highly enriched at nerve terminals. KIF2 suppression also produces a dramatic inhibition of neurite outgrowth; this phenomenon occurs after betagc has disappeared from growth cones. Taken collectively, our results suggest an important role for KIF2 in neurite extension, a phenomenon that may be related with the anterograde transport of a type of nonsynaptic vesicle that contains as one of its components a growth cone membrane receptor for IGF-1, a growth factor implicated in nerve cell development.

MeSH Terms
Amyloid beta-Protein Precursor/analysis Animals Antibodies, Monoclonal Cerebral Cortex/chemistry GAP-43 Protein Kinesins/analysis,genetics,immunology,physiology Membrane Glycoproteins/analysis Nerve Growth Factors/pharmacology Nerve Tissue Proteins/analysis Neurites/physiology Neurons/cytology,physiology Oligonucleotides, Antisense/pharmacology Organelles/chemistry,metabolism PC12 Cells Rats Receptor, IGF Type 1/analysis Subcellular Fractions/chemistry Synapsins/analysis Synaptic Vesicles/chemistry,metabolism Synaptophysin/analysis Thionucleotides/pharmacology Up-Regulation
Chemicals
Amyloid beta-Protein Precursor Antibodies, Monoclonal GAP-43 Protein Membrane Glycoproteins Nerve Growth Factors Nerve Tissue Proteins Oligonucleotides, Antisense Synapsins Synaptophysin Thionucleotides Receptor, IGF Type 1 Kinesins
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Morfini G
Instituto Investigación Médica Mercedes y Martín Ferreyra, 5000 Córdoba, Argentina.
Quiroga S
Rosa A
Kosik K
Cáceres A
References (53)
53 references, click to expand
  1. Cytoskeletal dynamics and nerve growth.
    Neuron. 1988 Nov;1(9):761-72 PMID: 3078414
  2. Rapid changes in the distribution of GAP-43 correlate with the expression of neuronal polarity during normal development and under experimental conditions.
    J Cell Biol. 1990 Apr;110(4):1319-31 PMID: 2139034
  3. Making the connection: cytoskeletal rearrangements during growth cone guidance.
    Cell. 1995 Oct 20;83(2):171-6 PMID: 7585934
  4. Radial extension of macrophage tubular lysosomes supported by kinesin.
    Nature. 1990 Aug 30;346(6287):864-6 PMID: 1697403
  5. KIF3A/B: a heterodimeric kinesin superfamily protein that works as a microtubule plus end-directed motor for membrane organelle transport.
    J Cell Biol. 1995 Sep;130(6):1387-99 PMID: 7559760
  6. Organelle transport along microtubules - the role of KIFs.
    Trends Cell Biol. 1996 Apr;6(4):135-41 PMID: 15157476
  7. Axonal transport and the cytoskeleton.
    Curr Opin Neurobiol. 1993 Oct;3(5):724-31 PMID: 8260821
  8. Transient IGF-I gene expression during the maturation of functionally related central projection neurons.
    J Neurosci. 1991 Nov;11(11):3442-55 PMID: 1658250
  9. The distribution of synapsin I and synaptophysin in hippocampal neurons developing in culture.
    J Neurosci. 1991 Jun;11(6):1617-26 PMID: 1904480
  10. Identification of kinesin in sea urchin eggs, and evidence for its localization in the mitotic spindle.
    Nature. 1985 Dec 5-11;318(6045):483-6 PMID: 2933590
  11. Identification and partial characterization of mitotic centromere-associated kinesin, a kinesin-related protein that associates with centromeres during mitosis.
    J Cell Biol. 1995 Jan;128(1-2):95-104 PMID: 7822426
  12. Nerve growth factor-induced neurite outgrowth in PC12 cells involves the coordinate induction of microtubule assembly and assembly-promoting factors.
    J Cell Biol. 1985 Nov;101(5 Pt 1):1799-807 PMID: 2997236
  13. The state of the art in antisense research.
    Nat Med. 1995 Nov;1(11):1116-8 PMID: 7584973
  14. MAP-1B/TAU functional redundancy during laminin-enhanced axonal growth.
    J Cell Sci. 1996 Feb;109 ( Pt 2):467-77 PMID: 8838670
  15. Regulation of peripheral nerve regeneration by insulin-like growth factors.
    Ann N Y Acad Sci. 1993 Aug 27;692:172-82 PMID: 8215021
  16. Heterogeneity of microtubule-associated protein 2 during rat brain development.
    Proc Natl Acad Sci U S A. 1984 Sep;81(17):5613-7 PMID: 6591209
  17. Intraneuronal compartments of the amyloid precursor protein.
    J Neurosci. 1993 Jul;13(7):3112-23 PMID: 8331388
  18. KIF3A is a new microtubule-based anterograde motor in the nerve axon.
    J Cell Biol. 1994 Jun;125(5):1095-107 PMID: 7515068
  19. Sense and antisense transfection analysis of tau function: tau influences net microtubule assembly, neurite outgrowth and neuritic stability.
    J Cell Sci. 1994 Apr;107 ( Pt 4):869-79 PMID: 8056843
  20. Organelle, bead, and microtubule translocations promoted by soluble factors from the squid giant axon.
    Cell. 1985 Mar;40(3):559-69 PMID: 2578887
  21. Trafficking of cell surface beta-amyloid precursor protein: retrograde and transcytotic transport in cultured neurons.
    J Cell Biol. 1995 Apr;129(2):431-42 PMID: 7721945
  22. Brain neurons develop in a serum and glial free environment: effects of transferrin, insulin, insulin-like growth factor-I and thyroid hormone on neuronal survival, growth and differentiation.
    Brain Res. 1987 Mar 17;406(1-2):32-42 PMID: 3105814
  23. Inhibition of kinesin-driven microtubule motility by monoclonal antibodies to kinesin heavy chains.
    J Cell Biol. 1988 Dec;107(6 Pt 2):2657-67 PMID: 2974459
  24. Insulin-like growth factor I receptors of fetal brain are enriched in nerve growth cones and contain a beta-subunit variant.
    Proc Natl Acad Sci U S A. 1995 May 9;92(10):4309-12 PMID: 7753803
  25. Point mutation of adenosine triphosphate-binding motif generated rigor kinesin that selectively blocks anterograde lysosome membrane transport.
    J Cell Biol. 1995 Nov;131(4):1039-53 PMID: 7490281
  26. KIFC2 is a novel neuron-specific C-terminal type kinesin superfamily motor for dendritic transport of multivesicular body-like organelles.
    Neuron. 1997 Mar;18(3):425-38 PMID: 9115736
  27. Establishment of a noradrenergic clonal line of rat adrenal pheochromocytoma cells which respond to nerve growth factor.
    Proc Natl Acad Sci U S A. 1976 Jul;73(7):2424-8 PMID: 1065897
  28. Insulin-like growth factor I receptor primary structure: comparison with insulin receptor suggests structural determinants that define functional specificity.
    EMBO J. 1986 Oct;5(10):2503-12 PMID: 2877871
  29. KIF2 is a new microtubule-based anterograde motor that transports membranous organelles distinct from those carried by kinesin heavy chain or KIF3A/B.
    J Cell Biol. 1995 Apr;129(1):157-67 PMID: 7535303
  30. Kinesin-mediated organelle translocation revealed by specific cellular manipulations.
    J Cell Biol. 1994 Nov;127(4):1021-39 PMID: 7962067
  31. Nerve growth factor regulates both the phosphorylation and steady-state levels of microtubule-associated protein 1.2 (MAP1.2).
    J Cell Biol. 1988 May;106(5):1573-81 PMID: 3372590
  32. Mice carrying null mutations of the genes encoding insulin-like growth factor I (Igf-1) and type 1 IGF receptor (Igf1r).
    Cell. 1993 Oct 8;75(1):59-72 PMID: 8402901
  33. The nature of the trophic action of brain-derived neurotrophic factor, des(1-3)-insulin-like growth factor-1, and basic fibroblast growth factor on mesencephalic dopaminergic neurons developing in culture.
    Neuroscience. 1993 Feb;52(4):855-66 PMID: 8095710
  34. A novel brain ATPase with properties expected for the fast axonal transport motor.
    Nature. 1985 Sep 5-11;317(6032):73-5 PMID: 2412134
  35. PC12 pheochromocytoma cells: culture, nerve growth factor treatment, and experimental exploitation.
    Methods Enzymol. 1987;147:207-16 PMID: 3670084
  36. Attenuation of microtubule-associated protein 1B expression by antisense oligodeoxynucleotides inhibits initiation of neurite outgrowth.
    Neuroscience. 1993 Feb;52(3):489-96 PMID: 8450955
  37. A taxol-dependent procedure for the isolation of microtubules and microtubule-associated proteins (MAPs).
    J Cell Biol. 1982 Feb;92(2):435-42 PMID: 6120944
  38. Inhibition of neurite polarity by tau antisense oligonucleotides in primary cerebellar neurons.
    Nature. 1990 Feb 1;343(6257):461-3 PMID: 2105469
  39. Suppression of kinesin expression in cultured hippocampal neurons using antisense oligonucleotides.
    J Cell Biol. 1992 May;117(3):595-606 PMID: 1533397
  40. Nerve sprouting in innervated adult skeletal muscle induced by exposure to elevated levels of insulin-like growth factors.
    J Cell Biol. 1990 Apr;110(4):1307-17 PMID: 2157718
  41. Characterization of KIFC2, a neuronal kinesin superfamily member in mouse.
    Neuron. 1997 Mar;18(3):439-51 PMID: 9115737
  42. XKCM1: a Xenopus kinesin-related protein that regulates microtubule dynamics during mitotic spindle assembly.
    Cell. 1996 Jan 12;84(1):37-47 PMID: 8548824
  43. Kinesin-related gene unc-104 is required for axonal transport of synaptic vesicles in C. elegans.
    Cell. 1991 May 31;65(5):837-47 PMID: 1710172
  44. The emerging kinesin family of microtubule motor proteins.
    Trends Biochem Sci. 1991 Jun;16(6):221-5 PMID: 1832505
  45. Kinesin family in murine central nervous system.
    J Cell Biol. 1992 Dec;119(5):1287-96 PMID: 1447303
  46. An actin-associated protein present in the microtubule organizing center and the growth cones of PC-12 cells.
    J Neurosci. 1992 Mar;12(3):750-61 PMID: 1372044
  47. The kinesin superfamily: tails of functional redundancy.
    Trends Cell Biol. 1991 Oct;1(4):93-8 PMID: 14731795
  48. KIF1B, a novel microtubule plus end-directed monomeric motor protein for transport of mitochondria.
    Cell. 1994 Dec 30;79(7):1209-20 PMID: 7528108
  49. The neuron-specific kinesin superfamily protein KIF1A is a unique monomeric motor for anterograde axonal transport of synaptic vesicle precursors.
    Cell. 1995 Jun 2;81(5):769-80 PMID: 7539720
  50. Expression and distribution of IGF-1 receptors containing a beta-subunit variant (betagc) in developing neurons.
    J Neurosci. 1997 Feb 15;17(4):1447-59 PMID: 9006986
  51. Subcellular distribution in cerebral cortex of two proteins phosphorylated by a cAMP-dependent protein kinase.
    J Cell Biol. 1979 Nov;83(2 Pt 1):308-19 PMID: 227912
  52. Growth of a rat neuroblastoma cell line in serum-free supplemented medium.
    Proc Natl Acad Sci U S A. 1979 Jan;76(1):514-7 PMID: 284369
  53. Transfection of PC12 cells with the human GAP-43 gene: effects on neurite outgrowth and regeneration.
    Brain Res Mol Brain Res. 1990 Jan;7(1):39-44 PMID: 2153893
Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.138.3.657
Published
1997-08-11
Pages
657-69
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2141628
Subset
IM
External Links
PubMed source DOI: 10.1083/jcb.138.3.657 PMC Full Text View journal details
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