Journal article
Enzymatic properties and regulation of the native isozymes of retinal membrane guanylyl cyclase (RetGC) from mouse photoreceptors
Biochemistry (Easton), v 50(25), pp 5590-5600
28 Jun 2011
PMID: 21598940
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Mouse photoreceptor function and survival critically depend on Ca
2+
-regulated retinal membrane guanylyl cyclase (RetGC), comprised of two isozymes, RetGC1 and RetGC2. We characterized the content, catalytic constants and regulation of native RetGC1 and RetGC2 isozymes using mice lacking guanylyl cyclase activating proteins GCAP1 and GCAP2 and deficient for either
GUCY2F
or
GUCY2E
genes, respectively. We found that the characteristics of both native RetGC isozymes were considerably different from other reported estimates made for mammalian RetGCs: the content of RetGC1 per mouse rod outer segments (ROS) was at least 3-fold lower, the molar ratio (RetGC2:RetGC1) 6-fold higher, and the catalytic constants of both GCAP-activated isozymes between 12 and 19-fold higher than previously measured in bovine ROS. The native RetGC isozymes had different basal activity and were accelerated 5 to 28-fold at physiological concentrations of GCAPs. RetGC2 alone was capable of contributing as much as 135-165 μM cGMP s
−1
or almost 23-28% to the maximal cGMP synthesis rate in mouse ROS. At the maximal level of activation by GCAP, this isozyme alone could provide a significantly high rate of cGMP synthesis compared to what is expected for normal recovery of a mouse rod, and this can help explain some of the unresolved paradoxes of rod physiology. GCAP-activated native RetGC1 and RetGC2 were less sensitive to inhibition by Ca
2+
in the presence of GCAP1 (EC
50Ca
~132-139 nM) than GCAP2 (EC
50Ca
~50-59 nM), thus arguing that Ca
2+
sensor properties of GCAP in a functional RetGC/GCAP complex are defined not by a particular target isozyme but the intrinsic properties of GCAPs themselves.
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Details
- Title
- Enzymatic properties and regulation of the native isozymes of retinal membrane guanylyl cyclase (RetGC) from mouse photoreceptors
- Creators
- Igor V. Peshenko - Drexel University Elkins Park CampusElena V. Olshevskaya - Drexel University Elkins Park CampusAndrey B. Savchenko - Drexel University Elkins Park CampusSukanya Karan - University of UtahKrzysztof Palczewski - Case Western Reserve UniversityWolfgang Baehr - University of UtahAlexander M. Dizhoor - Drexel University Elkins Park Campus
- Publication Details
- Biochemistry (Easton), v 50(25), pp 5590-5600
- Publisher
- American Chemical Society (ACS)
- Number of pages
- 11
- Grant note
- R01 EY011522-15 || EY / National Eye Institute : NEI R01 EY008061-26 || EY / National Eye Institute : NEI
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy; Pennsylvania College of Optometry (PCO)
- Web of Science ID
- WOS:000291897000005
- Scopus ID
- 2-s2.0-79959428038
- Other Identifier
- 991022035114604721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology