Limits...
Investigating neuronal function with optically controllable proteins.

Zhou XX, Pan M, Lin MZ - Front Mol Neurosci (2015)

Bottom Line: For example, neurite extension and synaptogenesis both involve localized and transient activation of cytoskeletal and signaling proteins, allowing changes in microarchitecture to occur rapidly and in a localized manner.These tools have demonstrated versatility in controlling various proteins and thereby cellular functions, and possess enormous potential for future applications in nervous systems.Just as optogenetic control of neuronal firing using opsins has changed how we investigate the function of cellular circuits in vivo, optical control may yet yield another revolution in how we study the circuitry of intracellular signaling in the brain.

View Article: PubMed Central - PubMed

Affiliation: Department of Bioengineering, Stanford University Stanford, CA, USA.

ABSTRACT
In the nervous system, protein activities are highly regulated in space and time. This regulation allows for fine modulation of neuronal structure and function during development and adaptive responses. For example, neurite extension and synaptogenesis both involve localized and transient activation of cytoskeletal and signaling proteins, allowing changes in microarchitecture to occur rapidly and in a localized manner. To investigate the role of specific protein regulation events in these processes, methods to optically control the activity of specific proteins have been developed. In this review, we focus on how photosensory domains enable optical control over protein activity and have been used in neuroscience applications. These tools have demonstrated versatility in controlling various proteins and thereby cellular functions, and possess enormous potential for future applications in nervous systems. Just as optogenetic control of neuronal firing using opsins has changed how we investigate the function of cellular circuits in vivo, optical control may yet yield another revolution in how we study the circuitry of intracellular signaling in the brain.

No MeSH data available.


Blue light using flavin adenine dinucleotide (BLUF) domain-regulated adenylate cyclases.(A) The euPACα polypeptide is composed of two BLUF and two catalytic domains in the order BLUF1, C1, BLUF2, C2, and likely dimerizes or tetramerizes when expressed heterologously. The C1 and C2 catalytic domains associate to form the adenylate cyclase active site. BLUF domains N-terminal to each catalytic domain enhance catalysis in response to light. (B) The bPAC is composed of a single BLUF and a single catalytic domain, and likely dimerizes when expressed, so that an adenylate cyclase active site forms at the interface of the catalytic domains. The BLUF domain enhances catalysis in response to light.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4508517&req=5

Figure 2: Blue light using flavin adenine dinucleotide (BLUF) domain-regulated adenylate cyclases.(A) The euPACα polypeptide is composed of two BLUF and two catalytic domains in the order BLUF1, C1, BLUF2, C2, and likely dimerizes or tetramerizes when expressed heterologously. The C1 and C2 catalytic domains associate to form the adenylate cyclase active site. BLUF domains N-terminal to each catalytic domain enhance catalysis in response to light. (B) The bPAC is composed of a single BLUF and a single catalytic domain, and likely dimerizes when expressed, so that an adenylate cyclase active site forms at the interface of the catalytic domains. The BLUF domain enhances catalysis in response to light.

Mentions: Euglena gracilis expresses a photoactivated adenylate cyclase that consists of α and β subunits (euPACα and euPACβ), each of which contains two BLUF domains. Each subunit can be expressed in heterologous organisms to mediate light-induced cAMP production, with the α subunit showing higher activity (Figure 2A; Efetova and Schwarzel, 2015). In adult Drosophila, activation of euPACα throughout the brain resulted in hyperactivity and freezing, demonstrating some ability to modulate neuronal function (Schroder-Lang et al., 2007). In Drosophila larvae, illumination of euPACα-expressing olfactory receptor neurons (ORNs) mimicked odorant-induced ORN activation (Bellmann et al., 2010). Light stimulation of specific euPACα-expressing ORNs induced attractive or repellent behaviors, indicating that the attractive or repulsive behaviors are determined by the ORNs but not by the receptors which detect the odorants. In Caenorhabditis elegans, pre-synaptic cAMP signaling plays a vital role in the regulation of locomotion, and photoactivation of euPACα in cholinergic neurons resulted in a rise in swimming frequency and speed of locomotion, and a decrease in the number of backward locomotion episodes (Weissenberger et al., 2011).


Investigating neuronal function with optically controllable proteins.

Zhou XX, Pan M, Lin MZ - Front Mol Neurosci (2015)

Blue light using flavin adenine dinucleotide (BLUF) domain-regulated adenylate cyclases.(A) The euPACα polypeptide is composed of two BLUF and two catalytic domains in the order BLUF1, C1, BLUF2, C2, and likely dimerizes or tetramerizes when expressed heterologously. The C1 and C2 catalytic domains associate to form the adenylate cyclase active site. BLUF domains N-terminal to each catalytic domain enhance catalysis in response to light. (B) The bPAC is composed of a single BLUF and a single catalytic domain, and likely dimerizes when expressed, so that an adenylate cyclase active site forms at the interface of the catalytic domains. The BLUF domain enhances catalysis in response to light.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4508517&req=5

Figure 2: Blue light using flavin adenine dinucleotide (BLUF) domain-regulated adenylate cyclases.(A) The euPACα polypeptide is composed of two BLUF and two catalytic domains in the order BLUF1, C1, BLUF2, C2, and likely dimerizes or tetramerizes when expressed heterologously. The C1 and C2 catalytic domains associate to form the adenylate cyclase active site. BLUF domains N-terminal to each catalytic domain enhance catalysis in response to light. (B) The bPAC is composed of a single BLUF and a single catalytic domain, and likely dimerizes when expressed, so that an adenylate cyclase active site forms at the interface of the catalytic domains. The BLUF domain enhances catalysis in response to light.
Mentions: Euglena gracilis expresses a photoactivated adenylate cyclase that consists of α and β subunits (euPACα and euPACβ), each of which contains two BLUF domains. Each subunit can be expressed in heterologous organisms to mediate light-induced cAMP production, with the α subunit showing higher activity (Figure 2A; Efetova and Schwarzel, 2015). In adult Drosophila, activation of euPACα throughout the brain resulted in hyperactivity and freezing, demonstrating some ability to modulate neuronal function (Schroder-Lang et al., 2007). In Drosophila larvae, illumination of euPACα-expressing olfactory receptor neurons (ORNs) mimicked odorant-induced ORN activation (Bellmann et al., 2010). Light stimulation of specific euPACα-expressing ORNs induced attractive or repellent behaviors, indicating that the attractive or repulsive behaviors are determined by the ORNs but not by the receptors which detect the odorants. In Caenorhabditis elegans, pre-synaptic cAMP signaling plays a vital role in the regulation of locomotion, and photoactivation of euPACα in cholinergic neurons resulted in a rise in swimming frequency and speed of locomotion, and a decrease in the number of backward locomotion episodes (Weissenberger et al., 2011).

Bottom Line: For example, neurite extension and synaptogenesis both involve localized and transient activation of cytoskeletal and signaling proteins, allowing changes in microarchitecture to occur rapidly and in a localized manner.These tools have demonstrated versatility in controlling various proteins and thereby cellular functions, and possess enormous potential for future applications in nervous systems.Just as optogenetic control of neuronal firing using opsins has changed how we investigate the function of cellular circuits in vivo, optical control may yet yield another revolution in how we study the circuitry of intracellular signaling in the brain.

View Article: PubMed Central - PubMed

Affiliation: Department of Bioengineering, Stanford University Stanford, CA, USA.

ABSTRACT
In the nervous system, protein activities are highly regulated in space and time. This regulation allows for fine modulation of neuronal structure and function during development and adaptive responses. For example, neurite extension and synaptogenesis both involve localized and transient activation of cytoskeletal and signaling proteins, allowing changes in microarchitecture to occur rapidly and in a localized manner. To investigate the role of specific protein regulation events in these processes, methods to optically control the activity of specific proteins have been developed. In this review, we focus on how photosensory domains enable optical control over protein activity and have been used in neuroscience applications. These tools have demonstrated versatility in controlling various proteins and thereby cellular functions, and possess enormous potential for future applications in nervous systems. Just as optogenetic control of neuronal firing using opsins has changed how we investigate the function of cellular circuits in vivo, optical control may yet yield another revolution in how we study the circuitry of intracellular signaling in the brain.

No MeSH data available.