A remote control for calcium channels
Collaborative work among scientists from IBS (Center for Cognition and Sociality) and KAIST (Department of Biological Sciences) feature the development of light-responding calcium channel activator, which elevates cellular calcium levels and increases memory in the mouse brain.
As Morse code enables information to be transmitted as a series of on-off tones and clicks, which can be decoded into words and text, in a somewhat similar manner, calcium (Ca2+) signals are encoded as distinct patterns of input with varying amplitudes, frequencies, and durations. As (Ca2+) is involved in literally every single cellular process in our body, it has been tempting to manipulate intracellular (Ca2+) levels for research or therapeutic purposes.
Recently, in high profile work, researchers have succeeded in developing a blue-light-dependent endogenous (Ca2+) channel activator, named OptoSTIM1 (an optically activated STIM1 protein). In this work, a light-responsive oligomerization plant protein, Cryptochrome2, was conjugated with a (Ca2+) channel activator, STIM1, which binds to (Ca2+) channels only when oligomerized by themselves. Depending on the power and exposure time of blue-light, (Ca2+) levels in the cell could be quantitatively controlled; varied levels of (Ca2+) could be decoded into different functional outcomes, such as actin cytoskeleton remodeling or gene expression, just as different Morse codes patterns can be deciphered.
The broad utility of OptoSTIM1 has been proven through modulating (Ca2+) levels in various human and mouse cell lines, including human embryonic stem cells, potentially fostering advances in stem cell engineering. Additionally, (Ca2+) levels could be manipulated in live animals such as zebrafish or in the brains of mice where increases in (Ca2+) levels in neurons resulted in elevated learning capacity of mice, suggesting that (Ca2+) plays a significant role in the memory formation process.
Recent evidence suggests that abnormal (Ca2+) channel activity is involved in various human diseases; thus, the specific control of (Ca2+) channel by OptoSTIM1 will provide a robust cell- or animal-based screening platform for identifying drug candidates that target (Ca2+) channels. OptoSTIM1 also offers potential optogenetic therapeutic means to treat diseases associated with (Ca2+) deficiency.
“Optogenetic control of endogenous (Ca2+) channels in vivo”, Taeyoon Kyung*, Sangkyu Lee*, Jung Eun Kim, Taesup Cho, Hyerim Park, Yun-Mi Jeong, Dongkyu Kim, Anna Shin, Sungsoo Kim, Jinhee Baek, Jihoon Kim, Na Yeon Kim, Doyeon Woo, Sujin Chae, Cheol-Hee Kim, Hee-sup Shin, Yong-Mahn Han, Daesoo Kim, and Won Do Heo, Nat. Biotechnol. (Advanced Online Publication: 09/15/2015, selected as a cover article)
* lab webpage