Identification, characterization, and functional study of the two novel human members of the semaphorin gene family.
We cloned two novel human transmembrane semaphorins, (HSA)SEMA6C and (HSA)SEMA6D, that belong to the class VI subgroup of the semaphorin family. The genes for SEMA6C and SEMA6D are mapped on chromosome 1q12-21.1 and 15q21.1, respectively. Among the adult tissues, SEMA6C is expressed only in skeletal muscle, whereas SEMA6D is expressed abundantly in kidney, brain, and placenta and moderately in the heart and skeletal muscles. During murine development, neither SEMA6C nor SEMA6D was expressed in embryonic day 10.5 (E10.5) embryos, but both were highly expressed in the areas of the lateral ventricle, the striatum, the wall of the midbrain, the pons/midbrain junction, and the choroid plexus of E13 embryos. Were neurons, neither axons nor astrocytes, highly expressed both semaphorins. Three isoforms of SEMA6C and five isoforms of SEMA6D derived from alternative splicing were identified, and their expression was regulated in a tissue- and development-dependent manner. Deletion analysis indicated that a sema domain and a PSI domain are integrally necessary for correct post-translation modification and subcellular localization. The extracellular domain of SEMA6C inhibited axonal extension of nerve growth factor-differentiated PC12 cells and induced the growth cone collapse of chicken dorsal root ganglion, rat hippocampal neurons, and rat cortical neurons in a dose-responsive manner. SEMA6D acted like SEMA6C except it had no significant effect on the growth cones of rat cortical neurons.
Qu
Xianghu
X
Department of Genomics and Proteomics, Beijing Institute of Radiation Medicine, Chinese National Human Genome Center at Beijing.
Wei
Handong
H
Zhai
Yun
Y
Que
Haiping
H
Chen
Qian
Q
Tang
Fei
F
Wu
Yan
Y
Xing
Guichun
G
Zhu
Yunping
Y
Liu
Shaojun
S
Fan
Ming
M
He
Fuchu
F
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D019556:COS Cells; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D002884:Chromosomes, Human, Pair 15; D003001:Cloning, Molecular; D018076:DNA, Complementary; D006801:Humans; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D005810:Multigene Family; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016716:PC12 Cells; D051381:Rats; D039961:Semaphorins; D017386:Sequence Homology, Amino Acid
D018076:DNA, Complementary; D009419:Nerve Tissue Proteins; C504198:SEMA6C protein, human; D039961:Semaphorins