Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
J Biol Chem
2017 May 12;29219:7850-7865. doi: 10.1074/jbc.M116.768143.
Show Gene links
Show Anatomy links
An inducible amphipathic helix within the intrinsically disordered C terminus can participate in membrane curvature generation by peripherin-2/rds.
Milstein ML, Kimler VA, Ghatak C, Ladokhin AS, Goldberg AFX.
???displayArticle.abstract???
Peripherin-2/rds is required for biogenesis of vertebrate photoreceptor outer segment organelles. Its localization at the high-curvature rim domains of outer segment disk membranes suggests that it may act to shape these structures; however, the molecular function of this protein is not yet resolved. Here, we apply biochemical, biophysical, and imaging techniques to elucidate the role(s) played by the protein's intrinsically disordered C-terminal domain and an incipient amphipathic α-helix contained within it. We investigated a deletion mutant lacking only this α-helix in stable cell lines and Xenopus laevis photoreceptors. We also studied a soluble form of the full-length ∼7-kDa cytoplasmic C terminus in cultured cells and purified from Escherichia coli The α-helical motif was not required for protein biosynthesis, tetrameric subunit assembly, tetramer polymerization, localization at disk rims, interaction with GARP2, or the generation of membrane curvature. Interestingly, however, loss of the helical motif up-regulated membrane curvature generation in cellulo, introducing the possibility that it may regulate this activity in photoreceptors. Furthermore, the incipient α-helix (within the purified soluble C terminus) partitioned into membranes only when its acidic residues were neutralized by protonation. This suggests that within the context of full-length peripherin-2/rds, partitioning would most likely occur at a bilayer interfacial region, potentially adjacent to the protein's transmembrane domains. In sum, this study significantly strengthens the evidence that peripherin-2/rds functions directly to shape the high-curvature rim domains of the outer segment disk and suggests that the protein's C terminus may modulate membrane curvature-generating activity present in other protein domains.
Anderson,
Mammalian cones: disc shedding, phagocytosis, and renewal.
1978, Pubmed
Anderson,
Mammalian cones: disc shedding, phagocytosis, and renewal.
1978,
Pubmed Anderson,
Phospholipids of bovine outer segments.
1970,
Pubmed Batra-Safferling,
Glutamic acid-rich proteins of rod photoreceptors are natively unfolded.
2006,
Pubmed Boesze-Battaglia,
A soluble peripherin/Rds C-terminal polypeptide promotes membrane fusion and changes conformation upon membrane association.
2003,
Pubmed Boesze-Battaglia,
A peptide analogue to a fusion domain within photoreceptor peripherin/rds promotes membrane adhesion and depolarization.
2000,
Pubmed Boon,
The spectrum of retinal dystrophies caused by mutations in the peripherin/RDS gene.
2008,
Pubmed Chen,
Dynamic behavior of rod photoreceptor disks.
2002,
Pubmed Chen,
The N-Terminal Amphipathic Helix of Endophilin Does Not Contribute to Its Molecular Curvature Generation Capacity.
2016,
Pubmed Choi,
Regulation of thyroid hormone-induced development in vivo by thyroid hormone transporters and cytosolic binding proteins.
2015,
Pubmed Clarke,
Rom-1 is required for rod photoreceptor viability and the regulation of disk morphogenesis.
2000,
Pubmed Colville,
Primary structure and expression of the human beta-subunit and related proteins of the rod photoreceptor cGMP-gated channel.
1996,
Pubmed Ding,
The R172W mutation in peripherin/rds causes a cone-rod dystrophy in transgenic mice.
2004,
Pubmed Drin,
Amphipathic helices and membrane curvature.
2010,
Pubmed Edrington,
Peripherin-2: an intracellular analogy to viral fusion proteins.
2007,
Pubmed Falk,
Distinctive properties of the lamellar and disk-edge structures of the rod outer segment.
1969,
Pubmed Falk,
Changes in structure of the disks of retinal rods in hypotonic solutions.
1973,
Pubmed Fliesler,
Sterol composition of bovine retinal rod outer segment membranes and whole retinas.
1982,
Pubmed Goldberg,
An intramembrane glutamic acid governs peripherin/rds function for photoreceptor disk morphogenesis.
2007,
Pubmed Goldberg,
Defective subunit assembly underlies a digenic form of retinitis pigmentosa linked to mutations in peripherin/rds and rom-1.
1996,
Pubmed Goldberg,
Expression and characterization of peripherin/rds-rom-1 complexes and mutants implicated in retinal degenerative diseases.
2000,
Pubmed Goldberg,
Folding and subunit assembly of photoreceptor peripherin/rds is mediated by determinants within the extracellular/intradiskal EC2 domain: implications for heterogeneous molecular pathologies.
2001,
Pubmed Goldberg,
Molecular basis for photoreceptor outer segment architecture.
2016,
Pubmed Goldberg,
Subunit composition of the peripherin/rds-rom-1 disk rim complex from rod photoreceptors: hydrodynamic evidence for a tetrameric quaternary structure.
1996,
Pubmed Goldberg,
Heterologous expression of photoreceptor peripherin/rds and Rom-1 in COS-1 cells: assembly, interactions, and localization of multisubunit complexes.
1995,
Pubmed Goldberg,
Cysteine residues of photoreceptor peripherin/rds: role in subunit assembly and autosomal dominant retinitis pigmentosa.
1998,
Pubmed Hu,
Membrane proteins of the endoplasmic reticulum induce high-curvature tubules.
2008,
Pubmed Hüttl,
Impaired channel targeting and retinal degeneration in mice lacking the cyclic nucleotide-gated channel subunit CNGB1.
2005,
Pubmed Kedzierski,
Deficiency of rds/peripherin causes photoreceptor death in mouse models of digenic and dominant retinitis pigmentosa.
2001,
Pubmed Kennedy,
What drives cell morphogenesis: a look inside the vertebrate photoreceptor.
2009,
Pubmed Kevany,
Structural and functional analysis of the native peripherin-ROM1 complex isolated from photoreceptor cells.
2013,
Pubmed Khattree,
Membrane curvature generation by a C-terminal amphipathic helix in peripherin-2/rds, a tetraspanin required for photoreceptor sensory cilium morphogenesis.
2013,
Pubmed Kyrychenko,
Lipid headgroups modulate membrane insertion of pHLIP peptide.
2015,
Pubmed Ladokhin,
CD spectroscopy of peptides and proteins bound to large unilamellar vesicles.
2010,
Pubmed Ladokhin,
How to measure and analyze tryptophan fluorescence in membranes properly, and why bother?
2000,
Pubmed Lee,
Characterization of peripherin/rds and rom-1 transport in rod photoreceptors of transgenic and knockout animals.
2006,
Pubmed
,
Xenbase Loewen,
The role of subunit assembly in peripherin-2 targeting to rod photoreceptor disk membranes and retinitis pigmentosa.
2003,
Pubmed
,
Xenbase Loewen,
Disulfide-mediated oligomerization of Peripherin/Rds and Rom-1 in photoreceptor disk membranes. Implications for photoreceptor outer segment morphogenesis and degeneration.
2000,
Pubmed MacDonald,
Small-volume extrusion apparatus for preparation of large, unilamellar vesicles.
1991,
Pubmed Molday,
Peripherin. A rim-specific membrane protein of rod outer segment discs.
1987,
Pubmed Molday,
Photoreceptors at a glance.
2015,
Pubmed Ogino,
High-throughput transgenesis in Xenopus using I-SceI meganuclease.
2006,
Pubmed
,
Xenbase Poetsch,
The cGMP-gated channel and related glutamic acid-rich proteins interact with peripherin-2 at the rim region of rod photoreceptor disc membranes.
2001,
Pubmed Posokhov,
Is lipid bilayer binding a common property of inhibitor cysteine knot ion-channel blockers?
2007,
Pubmed Ritter,
In situ visualization of protein interactions in sensory neurons: glutamic acid-rich proteins (GARPs) play differential roles for photoreceptor outer segment scaffolding.
2011,
Pubmed
,
Xenbase Ritter,
Predicted and measured disorder in peripherin/rds, a retinal tetraspanin.
2005,
Pubmed Ritter,
Uncoupling of photoreceptor peripherin/rds fusogenic activity from biosynthesis, subunit assembly, and targeting: a potential mechanism for pathogenic effects.
2004,
Pubmed
,
Xenbase Salinas,
A single valine residue plays an essential role in peripherin/rds targeting to photoreceptor outer segments.
2013,
Pubmed
,
Xenbase Shibata,
The reticulon and DP1/Yop1p proteins form immobile oligomers in the tubular endoplasmic reticulum.
2008,
Pubmed
,
Xenbase Shibata,
Mechanisms shaping the membranes of cellular organelles.
2009,
Pubmed Simunovic,
How curvature-generating proteins build scaffolds on membrane nanotubes.
2016,
Pubmed Snider,
MPEx: a tool for exploring membrane proteins.
2009,
Pubmed Steinberg,
Disc morphogenesis in vertebrate photoreceptors.
1980,
Pubmed Stuck,
Retinal Degeneration Slow (RDS) Glycosylation Plays a Role in Cone Function and in the Regulation of RDS·ROM-1 Protein Complex Formation.
2015,
Pubmed Stuck,
PRPH2/RDS and ROM-1: Historical context, current views and future considerations.
2016,
Pubmed Tam,
Generation of transgenic X. laevis models of retinal degeneration.
2013,
Pubmed
,
Xenbase Tam,
The C terminus of peripherin/rds participates in rod outer segment targeting and alignment of disk incisures.
2004,
Pubmed
,
Xenbase Teixeira,
pK(a) Values of Titrable Amino Acids at the Water/Membrane Interface.
2016,
Pubmed Tian,
An unconventional secretory pathway mediates the cilia targeting of peripherin/rds.
2014,
Pubmed
,
Xenbase Travis,
Complete rescue of photoreceptor dysplasia and degeneration in transgenic retinal degeneration slow (rds) mice.
1992,
Pubmed Vargas-Uribe,
Thermodynamics of Membrane Insertion and Refolding of the Diphtheria Toxin T-Domain.
2015,
Pubmed Vargas-Uribe,
Comparison of membrane insertion pathways of the apoptotic regulator Bcl-xL and the diphtheria toxin translocation domain.
2013,
Pubmed Veleri,
Biology and therapy of inherited retinal degenerative disease: insights from mouse models.
2015,
Pubmed Wensel,
Structural and molecular bases of rod photoreceptor morphogenesis and disease.
2016,
Pubmed Wensel,
Signal transducing membrane complexes of photoreceptor outer segments.
2008,
Pubmed Westrate,
Form follows function: the importance of endoplasmic reticulum shape.
2015,
Pubmed Wright,
Intrinsically disordered proteins in cellular signalling and regulation.
2015,
Pubmed Young,
Visual cells and the concept of renewal.
1976,
Pubmed Zhang,
Knockout of GARPs and the β-subunit of the rod cGMP-gated channel disrupts disk morphogenesis and rod outer segment structural integrity.
2009,
Pubmed Zurek,
Reticulon short hairpin transmembrane domains are used to shape ER tubules.
2011,
Pubmed
