Aryl Hydrocarbon Receptor-interacting Protein-like 1 Is an Obligate Chaperone of Phosphodiesterase 6 and Is Assisted by the γ-Subunit of Its Client

Kota N Gopalakrishna; Kimberly Boyd; Ravi P Yadav; Nikolai O Artemyev

doi:10.1074/jbc.M116.737593

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Aryl Hydrocarbon Receptor-interacting Protein-like 1 Is an Obligate Chaperone of Phosphodiesterase 6 and Is Assisted by the γ-Subunit of Its Client

Journal article

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Aryl Hydrocarbon Receptor-interacting Protein-like 1 Is an Obligate Chaperone of Phosphodiesterase 6 and Is Assisted by the γ-Subunit of Its Client

Kota N Gopalakrishna, Kimberly Boyd, Ravi P Yadav and Nikolai O Artemyev

The Journal of biological chemistry, Vol.291(31), pp.16282-16291

07/29/2016

DOI: 10.1074/jbc.M116.737593

PMCID: PMC4965576

PMID: 27268253

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Abstract

Phosphodiesterase 6 (PDE6) is the effector enzyme in the phototransduction cascade and is critical for the health of both rod and cone photoreceptors. Its dysfunction, caused by mutations in either the enzyme itself or AIPL1 (aryl hydrocarbon receptor-interacting protein-like 1), leads to retinal diseases culminating in blindness. Progress in research on PDE6 and AIPL1 has been severely hampered by failure to express functional PDE6 in a heterologous expression system. Here, we demonstrated that AIPL1 is an obligate chaperone of PDE6 and that it enables low yield functional folding of cone PDE6C in cultured cells. We further show that the AIPL1-mediated production of folded PDE6C is markedly elevated in the presence of the inhibitory Pγ-subunit of PDE6. As illustrated in this study, a simple and sensitive system in which AIPL1 and Pγ are co-expressed with PDE6 represents an effective tool for probing structure-function relationships of AIPL1 and reliably establishing the pathogenicity of its variants.

Retinal Diseases - genetics

Cyclic Nucleotide Phosphodiesterases, Type 6 - metabolism

Molecular Chaperones - metabolism

Humans

Molecular Chaperones - genetics

Cercopithecus aethiops

Retinal Diseases - metabolism

Cyclic Nucleotide Phosphodiesterases, Type 6 - genetics

Animals

Adaptor Proteins, Signal Transducing - genetics

HEK293 Cells

Mice

Adaptor Proteins, Signal Transducing - metabolism

COS Cells

Details

Title: Subtitle: Aryl Hydrocarbon Receptor-interacting Protein-like 1 Is an Obligate Chaperone of Phosphodiesterase 6 and Is Assisted by the γ-Subunit of Its Client
Creators: Kota N Gopalakrishna - From the Departments of Molecular Physiology and Biophysics and
Kimberly Boyd - From the Departments of Molecular Physiology and Biophysics and
Ravi P Yadav - From the Departments of Molecular Physiology and Biophysics and
Nikolai O Artemyev - From the Departments of Molecular Physiology and Biophysics and Ophthalmology and Visual Sciences, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242 nikolai-artemyev@uiowa.edu
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.291(31), pp.16282-16291
DOI: 10.1074/jbc.M116.737593
PMID: 27268253
PMCID: PMC4965576
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: United States
Grant note: R01 EY010843 / NEI NIH HHS
Language: English
Date published: 07/29/2016
Academic Unit: Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Ophthalmology and Visual Sciences
Record Identifier: 9984025348002771

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