The Dual Characteristics of Light-Induced Cryptochrome
2, Homo-oligomerization and Heterodimerization, for Optogenetic Manipulation
in Mammalian Cells
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Abstract
The photoreceptor cryptochrome 2
(CRY2) has become a powerful optogenetic
tool that allows light-inducible manipulation of various signaling
pathways and cellular processes in mammalian cells with high spatiotemporal
precision and ease of application. However, it has also been shown
that the behavior of CRY2 under blue light is complex, as the photoexcited
CRY2 can both undergo homo-oligomerization and heterodimerization
by binding to its dimerization partner CIB1. To better understand
the light-induced CRY2 activities in mammalian cells, this article
systematically characterizes CRY2 homo-oligomerization in different
cellular compartments, as well as how CRY2 homo-oligomerization and
heterodimerization activities affect each other. Quantitative analysis
reveals that membrane-bound CRY2 has drastically enhanced oligomerization
activity compared to that of its cytoplasmic form. While CRY2 homo-oligomerization
and CRY2-CIB1 heterodimerization could happen concomitantly, the presence
of certain CIB1 fusion proteins can suppress CRY2 homo-oligomerization.
However, the homo-oligomerization of cytoplasmic CRY2 can be significantly
intensified by its recruitment to the membrane via interaction with
the membrane-bound CIB1. These results contribute to the understanding
of the light-inducible CRY2-CRY2 and CRY2-CIB1 interaction systems
and can be used as a guide to establish new strategies utilizing the
dual optogenetic characteristics of CRY2 to probe cellular processes