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Journal article
A Role for GCAP2 in Regulating the Photoresponse: GUANYLYL CYCLASE ACTIVATION AND ROD ELECTROPHYSIOLOGY IN GUCA1B KNOCK-OUT MICE
The Journal of biological chemistry, v 283(43), pp 29135-29143
24 Oct 2008
PMID: 18723510
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Abstract
Cyclic GMP serves as the second messenger in visual transduction, linking
photon absorption by rhodopsin to the activity of ion channels. Synthesis of
cGMP in photoreceptors is supported by a pair of retina-specific guanylyl
cyclases, retGC1 and -2. Two neuronal calcium sensors, GCAP1 and GCAP2, confer
Ca
2+
sensitivity to guanylyl cyclase activity, but the importance
and the contribution of each GCAP is controversial. To explore this issue, the
gene
GUCA1B
, coding for GCAP2, was disrupted in mice, and the
capacity for knock-out rods to regulate retGC and generate photoresponses was
tested. The knock-out did not compromise rod viability or alter outer segment
ultrastructure. Levels of retGC1, retGC2, and GCAP-1 expression did not
undergo compensatory changes, but the absence of GCAP2 affected guanylyl
cyclase activity in two ways; (
a
) the maximal rate of cGMP synthesis
at low [Ca
2+
] dropped 2-fold and (
b
) the half-maximal rate
of cGMP synthesis was attained at a higher than normal [Ca
2+
]. The
addition of an antibody raised against mouse GCAP2 produced similar effects on
the guanylyl cyclase activity in wild type retinas. Flash responses of GCAP2
knock-out rods recovered more slowly than normal. Knock-out rods became more
sensitive to flashes and to steps of illumination but tended to saturate at
lower intensities, as compared with wild type rods. Therefore, GCAP2
regulation of guanylyl cyclase activity quickens the recovery of flash and
step responses and adjusts the operating range of rods to higher intensities
of ambient illumination.
Metrics
Details
- Title
- A Role for GCAP2 in Regulating the Photoresponse
- Creators
- Clint L. Makino - Massachusetts Eye and Ear InfirmaryIgor V. Peshenko - Salus UniversityXiao-Hong Wen - Wayne State UniversityElena V. Olshevskaya - Salus UniversityRonald Barrett - Wayne State UniversityAlexander M. Dizhoor - Salus University
- Publication Details
- The Journal of biological chemistry, v 283(43), pp 29135-29143
- Publisher
- American Society for Biochemistry and Molecular Biology
- Number of pages
- 9
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy; Pennsylvania College of Optometry (PCO)
- Web of Science ID
- WOS:000260179900041
- Scopus ID
- 2-s2.0-57649223578
- Other Identifier
- 991022035111904721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology