QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, July 11, 2007, 27(28):7447-7458; doi:10.1523/JNEUROSCI.4266-06.2007

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (12) Citing Articles via Google Scholar Google Scholar Articles by Wu, G. Articles by Ledeen, R. W. Search for Related Content PubMed PubMed Citation Articles by Wu, G. Articles by Ledeen, R. W. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Hazardous Substances DB CALCIUM COMPOUNDS CALCIUM, ELEMENTAL

 Previous Article  |  Next Article 

Cellular/Molecular
Induction of Calcium Influx through TRPC5 Channels by Cross-Linking of GM1 Ganglioside Associated with 5ß1 Integrin Initiates Neurite Outgrowth

Gusheng Wu,¹ Zi-Hua Lu,¹ Alexander G. Obukhov,² Martha C. Nowycky,² and Robert W. Ledeen^1,2

Departments of ¹Neurology and Neurosciences and ²Physiology and Pharmacology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey 07103

Correspondence should be addressed to Dr. Gusheng Wu, Department of Neurology and Neurosciences, MSB-H506, New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103. Email: gwu{at}umdnj.edu

Previous studies demonstrated that cross-linking of GM1 ganglioside with multivalent ligands, such as B subunit of cholera toxin (CtxB), induced Ca²⁺ influx through an unidentified, voltage-independent channel in several cell types. Application of CtxB to undifferentiated NG108-15 cells resulted in outgrowth of axon-like neurites in a Ca²⁺ influx-dependent manner. In this study, we demonstrate that CtxB-induced Ca²⁺ influx is mediated by TRPC5 channels, naturally expressed in these cells and primary neurons. Both Ca²⁺ influx and neurite induction were blocked by TRPC5 small interfering RNA (siRNA). Pretreatment of NG108-15 cells with neuraminidase increased cell-surface GM1 and greatly enhanced the signal. GM1 was not directly associated with TRPC5 but rather with 5ß1 integrin, which opened the channel through a signaling sequence after cross-linking of the GM1/integrin complex. This cascade included autophosphorylation of focal adhesion kinase and subsequent activation of phospholipase C (PLC) and phosphoinositide-3 kinase [PI(3)K]. Pharmacological blockers that inhibited tyrosine kinase, PLC, and PI(3)K suppressed both CtxB-induced Ca²⁺ influx and neurite outgrowth. These were also suppressed by SK&F96365, a nonspecific transient receptor potential channel blocker. Confocal immunocytochemistry revealed that GM1 cross-linking induced colocalization of GM1 with these signaling elements in sprouting regions of plasma membrane. In primary cerebellar granular neurons (CGNs), TRPC5 was detected at 2 d in vitro (2 DIV), a stage corresponding to CtxB-stimulated Ca²⁺ influx. Neurite outgrowth in CGNs, determined at 3 DIV, was accelerated by CtxB and suppressed by TRPC5 siRNA and the above blockers. The crucial role of GM1 was indicated with CGNs from ganglio-series null mice, in which growth of axons was significantly retarded.

Key words: TRPC5 channel; GM1 ganglioside; calcium signaling; integrin; neuritogenesis; focal adhesion kinase

---

Received Sept. 29, 2006; revised May 18, 2007; accepted May 21, 2007.

Correspondence should be addressed to Dr. Gusheng Wu, Department of Neurology and Neurosciences, MSB-H506, New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103. Email: gwu{at}umdnj.edu

This article has been cited by other articles:

				J. J. Plomp and H. J. Willison Pathophysiological actions of neuropathy-related anti-ganglioside antibodies at the neuromuscular junction J. Physiol., August 15, 2009; 587(16): 3979 - 3999. [Abstract] [Full Text] [PDF]

				M. A. Davare, D. A. Fortin, T. Saneyoshi, S. Nygaard, S. Kaech, G. Banker, T. R. Soderling, and G. A. Wayman Transient Receptor Potential Canonical 5 Channels Activate Ca2+/Calmodulin Kinase I{gamma} to Promote Axon Formation in Hippocampal Neurons J. Neurosci., August 5, 2009; 29(31): 9794 - 9808. [Abstract] [Full Text] [PDF]

				G. Wu, X. Xie, Z.-H. Lu, and R. W. Ledeen Sodium-calcium exchanger complexed with GM1 ganglioside in nuclear membrane transfers calcium from nucleoplasm to endoplasmic reticulum PNAS, June 30, 2009; 106(26): 10829 - 10834. [Abstract] [Full Text] [PDF]

				J. Wang, Z.-H. Lu, H.-J. Gabius, C. Rohowsky-Kochan, R. W. Ledeen, and G. Wu Cross-Linking of GM1 Ganglioside by Galectin-1 Mediates Regulatory T Cell Activity Involving TRPC5 Channel Activation: Possible Role in Suppressing Experimental Autoimmune Encephalomyelitis J. Immunol., April 1, 2009; 182(7): 4036 - 4045. [Abstract] [Full Text] [PDF]

				J. Abramowitz and L. Birnbaumer Physiology and pathophysiology of canonical transient receptor potential channels FASEB J, February 1, 2009; 23(2): 297 - 328. [Abstract] [Full Text] [PDF]

				N. Ichikawa, K. Iwabuchi, H. Kurihara, K. Ishii, T. Kobayashi, T. Sasaki, N. Hattori, Y. Mizuno, K. Hozumi, Y. Yamada, et al. Binding of laminin-1 to monosialoganglioside GM1 in lipid rafts is crucial for neurite outgrowth J. Cell Sci., January 15, 2009; 122(2): 289 - 299. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help