2007 Fiscal Year Final Research Report Summary
Functional analyses of the constant region of CNR/protocadherin-a of the dustered protocadherins
| Project/Area Number |
17500211
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neuroscience in general
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| Research Institution | Fukuoka Women's University |
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Principal Investigator |
HAMADA Shun Fukuoka Women's University, Dept. of Human Environmental Science, Associate professor (60282349)
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| Project Period (FY) |
2005 – 2007
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| Keywords | cadherin / protocadherin / cell adhesion molecule / neuroscience / axon guidance / synapse formation / brain development |
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| Research Abstract |
Clustered protocadherins (Pcdhs) constitute the largest subgroup in the cadherin superfamily. About sixty members of clustered Pcdhs are produced from a unique gene cluster. According to the positions in this gene cluster, clustered protocadherins are further classified into three subfamilies, CNR/protocadherin-alpha (Pcdha), Pcdh-beta and Pcdh-gamma. Since clustered Pcdhs have been reported to localize at synapses and in developing axons, they have been assumed to play important roles in neural circuit formation and/or selective synapse formation. However, the functional roles of clustered Pcdhs have remained to be clarified. In this project, we focused on functions of the constant region, a common cytoplasmic region found in all Pcdha proteins.
1. Phenotype analyses of Pcdha mutant mice
Intense expression of Pcdha proteins in the olfactory sensory neurons (OSNs) prompted us to examine axonal projection of these neurons to the olfactory glomeruli in Pcdha mutant mice, in which the constant region exons had been deleted by gene targeting. In wild-type mice, OSNs that express a given odorant receptor gene project their axons to one glomerulus in each of the two halves of an olfactory bulb. In the Pcdha mutant mice, however, axonal sorting of OSN axons into glomeruli were perturbed, and multiple, small, extraneous glomeruli for the odorant receptors were observed.
2. Roles of the constant region in subcellular localization of Pcdha proteins.
Pcdha proteins have two alternative constant regions, A- and B-type. Overexpressed Pcdha proteins with A-type constant region are rarely transported to the plasma membrane. In this project, we examined which domain of the A-type constant region is responsible for the subcellular localization of Pcdha-A type proteins. Our results indicate that a lysine-rich domain near the carboxyl-terminus of A-type constant region interferes transport to the plasma membrane in cell lines and neurons.
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[Journal Article] The protocadherin-a family is involved in axonal coalescence of olfactory sensoryneurons into glomeruli of the olfactory bulb in mouse2008
Author(s)
Hasegawa S., Hamada, S. (co-first author), Kumode, Y., Katori, S., Fukuda, E., Uchiyama, Y., Hirabayasti, T., Mombaerts, P., Yagi, T.
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Journal Title
Molecular and Cellular Neuroscience 38
Pages: 66-79
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Presentation] Protocadherin-a family regulates axonal sorting into glomeruli in the mouse olfactory system2005
Author(s)
Hasegawa S, Hamada S, Kumode Y, Esumi S, Katori S, Uchiyama Y, Hirabayashi T, Mombaerts P, Yagi, T
Organizer
15th International Society of Developmental Biologists Congress 2005
Place of Presentation
Sydney, Australia
Year and Date
2005-09-06
Description
「研究成果報告書概要(欧文)」より
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