Guanylyl Cyclase Activating Protein

Gorczyca, Wojciech; Polans, Arthur S.; Surgucheva, Irina; Subbaraya, Iswari; Baehr, Wolfgang; Palczewski, Krzysztof

doi:10.1074/jbc.270.37.22029

Cited by 189 publications

(152 citation statements)

References 42 publications

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“…It has been observed (2, 41) that a nonacylated recombinant form of GCAP-1 had much lower (near 40-fold) affinity to RetGCs and lower Ca 2ϩ sensitivity compared with fatty acylated GCAP-1 (2). GCAP-1 and GCAP-2 are most closely related to each other, both genetically (48) and functionally (1,(7)(8)(9)(10)(11). Given our observations, it is not immediately apparent why such highly homologous proteins as GCAP-1 and GCAP-2 would demonstrate such a difference in terms of their dependence on fatty acylation.…”

Section: Fig 2 Expression Of Myristoylated and Nonacylated Recombinmentioning

confidence: 71%

“…21 and 22), both GCAPs interact with RetGC via the cyclase intracellular domain (23,24). GCAP-1 is able to stimulate recombinant RetGC-1 (11,24), while GCAP-2 stimulates both recombinant RetGC-1 and RetGC-2 (8,19,23). However, the question which of the two cyclases can be a target for any particular GCAP in vivo has not yet been properly addressed.…”

Section: Camentioning

confidence: 99%

“…At least two different GCAP-regulated RetGCs have been identified in mammalian photoreceptors, RetGC-1 (8, 14 -18) and RetGC-2 (19,20) (or GC-E and GC-F, respectively). It has been demonstrated by independent groups that GCAP-1 and GCAP-2 can activate RetGCs in OS membranes in vitro within the range of free Ca 2ϩ concentrations corresponding to the estimated physiological range (1,(7)(8)(9)(10)(11)(12)19). Unlike peptide ligands that regulate other known membrane guanylyl cyclases via the cyclase extracellular domains (reviewed in Refs.…”

Section: Camentioning

confidence: 99%

“…The estimate of the magnitude of this effect is that light lowers free intracellular Ca 2ϩ from a dark level of 500 nM to as low as 50 nM (6). The decrease in free Ca 2ϩ concentration allows guanylyl cyclase activator proteins (GCAPs) (7)(8)(9)(10)(11) to stimulate a membrane guanylyl cyclase (RetGC) (12,13). Two homologous GCAPs have been identified in the retina: GCAP-1 (7,9) and GCAP-2 (8,10).…”

Section: Camentioning

confidence: 99%

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Calcium Binding, but Not a Calcium-Myristoyl Switch, Controls the Ability of Guanylyl Cyclase-activating Protein GCAP-2 to Regulate Photoreceptor Guanylyl Cyclase

Olshevskaya¹,

Hughes²,

Hurley³

et al. 1997

Journal of Biological Chemistry

130

142

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We demonstrate that the N terminus of GCAP-2, like those of other members of the recoverin family of Ca 2؉-binding proteins, is fatty acylated. However, unlike other proteins of this family, more GCAP-2 is present in the membrane fraction at low Ca 2؉ than at high Ca 2؉ concentrations. We investigated the role of the N-terminal fatty acyl residue in the ability of GCAP-2 to regulate RetGCs. Myristoylated or nonacylated GCAP-2 forms were expressed in Escherichia coli. Wild-type GCAP-2 and the Gly 2 3 Ala 2 GCAP-2 mutant, which is unable to undergo N-terminal myristoylation, were also expressed in mammalian HEK293 cells. We found that compartmentalization of GCAP-2 in photoreceptor outer segment membranes is Ca 2؉ -and ionic strength-sensitive, but it does not require the presence of the fatty acyl group and does not necessarily directly reflect GCAP-2 interaction with RetGC. The lack of myristoylation does not significantly affect the ability of GCAP-2 to stimulate RetGC. Nor does it affect the ability of the Ca 2؉ -loaded form of GCAP-2 to compete with the GCAP-2 mutant that constitutively activates RetGC. We conclude that while Ca 2؉ binding plays a major regulatory role in GCAP-2 function, it does not operate through a calcium-myristoyl switch similar to the one found in recoverin.

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Section: Fig 2 Expression Of Myristoylated and Nonacylated Recombinmentioning

confidence: 71%

Section: Camentioning

confidence: 99%

Section: Camentioning

confidence: 99%

Section: Camentioning

confidence: 99%

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Calcium Binding, but Not a Calcium-Myristoyl Switch, Controls the Ability of Guanylyl Cyclase-activating Protein GCAP-2 to Regulate Photoreceptor Guanylyl Cyclase

Olshevskaya¹,

Hughes²,

Hurley³

et al. 1997

Journal of Biological Chemistry

130

142

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“…To study the involvement of these amino acids in substrate specificity, we mutated all three amino acids to their counterparts in AC, creating DdGCA kqd . (36,37).…”

Section: Regulation Of Ddgca Activity By Gtp␥s-mentioning

confidence: 99%

GTPγS Regulation of a 12-Transmembrane Guanylyl Cyclase Is Retained after Mutation to an Adenylyl Cyclase

Roelofs¹,

Loovers²,

Haastert

2001

Journal of Biological Chemistry

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DdGCA is a Dictyostelium guanylyl cyclase with a topology typical for mammalian adenylyl cyclases containing 12 transmembrane-spanning regions and two cyclase domain. In Dictyostelium cells heterotrimeric G-proteins are essential for guanylyl cyclase activation by extracellular cAMP. In lysates, guanylyl cyclase activity is strongly stimulated by guanosine 5-3-O-(thio) triphosphate (GTP␥S), which is also a substrate of the enzyme. DdGCA was converted to an adenylyl cyclase by introducing three point mutations. Expression of the obtained DdGCA kqd in adenylyl cyclase-defective cells restored the phenotype of the mutant. GTP␥S stimulated the adenylyl cyclase activity of DdGCA kqd with properties similar to those of the wild-type enzyme (decrease of K m and increase of V max ), demonstrating that GTP␥S stimulation is independent of substrate specificity. Furthermore, GTP␥S activation of DdGCA kqd is retained in several null mutants of G␣ and G␤ proteins, indicating that GTP␥S activation is not mediated by a heterotrimeric G-protein but possibly by a monomeric G-protein.

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New Mutation, P575L, in the GUCY2D Gene in a Family With Autosomal Dominant Progressive Cone Degeneration

Small¹

2008

Arch Ophthalmol

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To clinically characterize the retinal abnormalities and identify the mutation causing an autosomal dominant cone degeneration in an African American family. Methods: Clinical characterization of family members using fundus photography, fluorescein angiography, and electrophysiological testing. Standard molecular genetic methods were used, including segregation analysis and DNA sequencing of candidate genes. Genetic mutation screening was performed in 20 individuals: 10 clinically unaffected and 10 affected. Results: The affected family members had findings consistent with a primary cone degeneration. A novel mutation, P575L, was found in exon 8 of the GUCY2D gene in 12 members of this family. Conclusions: Inadditiontofindingapreviouslyundescribed mutation in GUCY2D, 2 of the family members who were thought to be unaffected through routine clinical examinations also had this mutation. These findings suggest that autosomal dominant cone degeneration in this family demonstrated age-dependent penetrance, which appears incomplete. This is the first African American family reported with a mutation in GUCY2D. Because the disease in this family and the one we previously described is primarily a cone degeneration, this disease should be more properly classified as cone degeneration and be called cone degeneration 2. Clinical Relevance: This study helps to expand the phenotype of the disease and help clinicians identify patients with cone degenerations.

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Guanylyl Cyclase Activating Protein

Cited by 189 publications

References 42 publications

Calcium Binding, but Not a Calcium-Myristoyl Switch, Controls the Ability of Guanylyl Cyclase-activating Protein GCAP-2 to Regulate Photoreceptor Guanylyl Cyclase

Calcium Binding, but Not a Calcium-Myristoyl Switch, Controls the Ability of Guanylyl Cyclase-activating Protein GCAP-2 to Regulate Photoreceptor Guanylyl Cyclase

GTPγS Regulation of a 12-Transmembrane Guanylyl Cyclase Is Retained after Mutation to an Adenylyl Cyclase

New Mutation, P575L, in the GUCY2D Gene in a Family With Autosomal Dominant Progressive Cone Degeneration

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