Increased Expression of the Dyslexia Candidate Gene DCDC2 Affects Length and Signaling of Primary Cilia in Neurons

被引:90
|
作者
Massinen, Satu [1 ,2 ]
Hokkanen, Marie-Estelle [3 ]
Matsson, Hans [4 ]
Tammimies, Kristiina [4 ]
Tapia-Paez, Isabel [4 ]
Dahlstrom-Heuser, Vanina [3 ]
Kuja-Panula, Juha [3 ]
Burghoorn, Jan [4 ,5 ]
Jeppsson, Kristian E. [4 ,5 ]
Swoboda, Peter [4 ,5 ]
Peyrard-Janvid, Myriam [4 ]
Toftgard, Rune [4 ]
Castren, Eero [3 ]
Kere, Juha [1 ,2 ,3 ,4 ,6 ]
机构
[1] Univ Helsinki, Res Programs Unit, Helsinki, Finland
[2] Univ Helsinki, Dept Med Genet, Helsinki, Finland
[3] Univ Helsinki, Ctr Neurosci, Helsinki, Finland
[4] Karolinska Inst, Dept Biosci & Nutr, Huddinge, Sweden
[5] Sodertorn Univ Coll, Sch Life Sci, Huddinge, Sweden
[6] Folkhalsan Inst Genet, Helsinki, Finland
来源
PLOS ONE | 2011年 / 6卷 / 06期
基金
瑞典研究理事会; 芬兰科学院;
关键词
HIPPOCAMPAL NEUROGENESIS; DCX SUPERFAMILY; NERVOUS-SYSTEM; C-ELEGANS; MIGRATION; BRAIN; DOUBLECORTIN; DYSFUNCTION; PROTEIN; KINASE;
D O I
10.1371/journal.pone.0020580
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
DCDC2 is one of the candidate susceptibility genes for dyslexia. It belongs to the superfamily of doublecortin domain containing proteins that bind to microtubules, and it has been shown to be involved in neuronal migration. We show that the Dcdc2 protein localizes to the primary cilium in primary rat hippocampal neurons and that it can be found within close proximity to the ciliary kinesin-2 subunit Kif3a. Overexpression of DCDC2 increases ciliary length and activates Shh signaling, whereas downregulation of Dcdc2 expression enhances Wnt signaling, consistent with a functional role in ciliary signaling. Moreover, DCDC2 overexpression in C. elegans causes an abnormal neuronal phenotype that can only be seen in ciliated neurons. Together our results suggest a potential role for DCDC2 in the structure and function of primary cilia.
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页数:10
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