Targeting SMN to Cajal bodies and nuclear gems during neuritogenesis
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Neurite outgrowth is a central feature of neuronal differentiation. PC12 cells are a good model system for studying the peripheral nervous system and the outgrowth of neurites. In addition to the dramatic changes observed in the cytoplasm, neuronal differentiation is also accompanied by striking changes in nuclear morphology. The large and sustained increase in nuclear transcription during neuronal differentiation requires synthesis of a large number of factors involved in pre-mRNA processing. We show that the number and composition of the nuclear subdomains called Cajal bodies and gems changes during the course of N-ras-induced neuritogenesis in the PC12-derived cell line UR61. The Cajal bodies found in undifferentiated cells are largely devoid of the survival of motor neurons (SMN) protein product. As cells shift to a differentiated state, SMN is not only globally upregulated, but is progressively recruited to Cajal bodies. Additional SMN foci (also known as Gemini bodies, gems) can also be detected. Using dual-immunogold labeling electron microscopy and mouse embryonic fibroblasts lacking the coilin protein, we show that gems clearly represent a distinct category of nuclear body.
KeywordsTyrosine Hydroxylase Nuclear Body Dexamethasone Treatment Cajal Body Tyrosine Hydroxylase Gene
This work was supported by grants from the following institutions: Centro de Investigación de Enfermedades Neurológicas (CIEN), Instituto de Salud Carlos III (Madrid, Spain); Dirección General de Investigacion of Spain (BFI2002-0454); the National Institutes of Health, USA (R01-NS41617 and R01-GM53034) and the Muscular Dystrophy Association, USA (RG 3290).
- Cajal SR (1910) El núcleo de las células piramidales del cerebro humano y de algunos mamíferos. Trab Lab Invest Biol 8:27–62Google Scholar
- Chao MV, Hempstead BL (1995) p75 and Trk: a two-receptor system. Trends Neurosci 18:321–326Google Scholar
- Guerrero I, Pellicer A, Burstein DE (1988) Dissociation of c-Fos from ODC expression and neuronal differentiation in a PC12 subline stably transfected with an inducible N-Ras oncogene. Biochem Biophys Res 150:1185–1192Google Scholar
- Kandel ER, Schwartz JH, Jessell TM (2000) Principles of neural science. McGraw-Hill Company, New YorkGoogle Scholar
- Peters A, Palay SL, Webster H de F (1991) The fine structure of the nervous system. Neurons and their supporting cells. Oxford University Press, New YorkGoogle Scholar
- Schul W, Groenhaut B, Koberna K, Takagaki Y, Jenny A, Manders EM, Raska I, van Driel R, de Jong L (1996) The RNA 3′ cleavage factors CstF 64 kDa and CPSF 100 kDa are concentrated in nuclear domains closely associated with coiled bodies and newly synthesized RNA. EMBO J 15:2883–2892PubMedGoogle Scholar
- Shpargel KB, Ospina JK, Tucker KE, Matera AG, Hebert MD (2003) Control of Cajal body number is mediated by the coilin C-terminus. J Cell Sci 14:9–16Google Scholar