Analyses of the functional domains in sugar chains using neuronal growth cones

2015 Fiscal Year Final Research Report

• Project Area: Deciphering sugar chain-based signals regulating integrative neuronal functions
• Project/Area Number: 23110005
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: TOJIMA Takuro 国立研究開発法人理化学研究所, 脳科学総合研究センター, 研究員 (00373332)
• Co-Investigator(Renkei-kenkyūsha): KAMIGUCHI Hiroyuki 理化学研究所, 脳科学総合研究センター, シニアチームリーダー (10233933) ; KUBOYAMA Tomoharu 富山大学, 和漢医薬学総合研究所, 助教 (10415151)
• Project Period (FY): 2011-04-01 – 2016-03-31
• Keywords: コンドロイチン硫酸 / ケラタン硫酸 / 軸索ガイダンス / 成長円錐 / cAMP / カルシウム

Outline of Final Research Achievements

Proteoglycans are extracellular macromolecules composed of a core protein and one or more covalently attached glycosaminoglycan (GAG) sugar chain(s). Recent discoveries of cell-surface GAG receptors led us to propose a novel concept that sugar chains act as physiological ligands that evoke various cellular responses. However, little is known about the intracellular signaling mechanisms downstream of GAG receptors. In this study, we examined whether chondroitin sulfate (CS) and keratan sulfate (KS) GAG chains affect motilities of neuronal growth cones and what signaling mechanisms mediate the growth cone behaviors. We found that extracellular gradients of CS-E and high-sulfated KS repelled growth cones of dorsal root ganglion neurons. The repulsion was dependent on intracellular calcium, and converted into attraction in the presence of higher concentration of cAMP. These results indicate that GAG chains act as bidirectional axon guidance cues in the developing nervous system.

Free Research Field

神経科学