The C-Terminal Region of Reelin: Structure and Function
Reelin is a very large secreted glycoprotein of about 3460 amino acids in mammalian species. Reelin is divided into three subdomains from its primary sequence (D’Arcangelo et al., 1995): the N-terminal F-spondin-like domain, the eight tandem of Reelin repeat, and the short and highly basic C-terminal region (CTR). The N-terminal F-spondin-like domain is proposed to be necessary and sufficient for multimerization of Reelin (Utsunomiya-Tate et al., 2000). The function of each Reelin repeat is not fully understood, but the region between the fifth and sixth repeat is sufficient for binding to the Reelin receptors, very-low-density lipoprotein receptor (VLDLR) and apolipoprotein receptor 2 (ApoER2) (Yasui et al., 2007). The CTR, which is about 30 amino acids long, comprises less than 1% of the whole Reelin protein.
The exact definition of CTR has not been determined and is closely related with the definition of Reelin repeat. In the original work that reported the first identification of mouse Reelin (D’Arcangelo et al., 1995), the eighth Reelin repeat was proposed to end at Val3427, making the last 34 amino acid residues CTR. The reason for choosing this boundary was not given. Subsequently, Ichihara et al. (2001) found some new repetitive units at its N-terminal region by computerized search and realigned the Reelin repeat. In their alignment, the eighth Reelin repeat ended at Val3429 (i.e., CTR = 32 amino acids, Ichihara et al., 2001). Deciding the boundary between the eighth Reelin repeat from the alignment of the amino acid sequence has limitations, and it should be determined by functional examinations. Hereafter in this chapter, we adopt the definition by Ichihara et al. (2001) solely to avoid confusion, and it should be noted that the exact definition of CTR is an open question. It is also worth mentioning that the results discussed in this chapter are unlikely to be affected by moving the boundary by a few amino acids.
KeywordsYellow Fluorescent Protein Primary Cortical Neuron Repetitive Unit Flag Epitope Reelin Gene
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