Tubulins in the primate retina: evidence that xanthophylls may be endogenous ligands for the paclitaxel-binding site.
The xanthophylls-lutein, zeaxanthin, and meso-zeaxanthin (L&Z)-are found in the central region of the primate retina, which is called the macula lutea (yellow spot). How they are anchored there and what their function is has been debated for over 50 years. Here, we present evidence that they may be bound to the paclitaxel (Taxol) binding site of the beta-tubulin subunit of microtubules and that a major function may be to modulate the dynamic instability of microtubules in the macula. Also, we compare nucleic acid and amino acid sequences of tubulins that are in human brain with those we have isolated from human-retina and monkey-macula cDNA libraries. In so doing, we suggest that in primates, class I beta-tubulin consists of at least two subtypes (beta(Ia) and beta(Ib)). Alignment analysis of the sequences of the genes for beta(Ia) and beta(Ib) indicates that the corresponding mRNAs may have other functions in addition to that of coding for proteins. Furthermore, we show that there are at least five different types of beta-tubulin in the macula lutea of rhesus monkey.
Crabtree
D V
DV
Schepens Eye Research Institute and Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA. crabtree@vision.eri.harvard.edu
Ojima
I
I
Geng
X
X
Adler
A J
AJ
D000470:Alkaloids / Q000494:pharmacology; D000473:Alkanes; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001665:Binding Sites; D002219:Carbamates; D002338:Carotenoids / Q000378:metabolism; D004224:Diterpenes; D034261:Epothilones; D004852:Epoxy Compounds / Q000494:pharmacology; D000882:Haplorhini; D006801:Humans; D007783:Lactones / Q000494:pharmacology; D008024:Ligands; D014975:Lutein / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017239:Paclitaxel / Q000494:pharmacology*; D011753:Pyrones; D012160:Retina / Q000187:drug effects* / Q000378:metabolism; D013844:Thiazoles / Q000494:pharmacology; D014404:Tubulin / Q000378:metabolism*
D000470:Alkaloids; D000473:Alkanes; D000972:Antineoplastic Agents, Phytogenic; D002219:Carbamates; D004224:Diterpenes; D034261:Epothilones; D004852:Epoxy Compounds; D007783:Lactones; D008024:Ligands; D011753:Pyrones; D013844:Thiazoles; D014404:Tubulin; C109551:eleutherobin; D002338:Carotenoids; C071229:discodermolide; D017239:Paclitaxel; C093788:epothilone B; D014975:Lutein