Evidence map›Paper›PMID 17962466›Full record

ArticleInvestigative ophthalmology & visual science2007

Identifying the role of specific motifs in the lens fiber cell specific intermediate filament phakosin.

Joshua T Pittenger, John F Hess, Paul G Fitzgerald

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Investigative ophthalmology & visual science, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.1field-weighted citation impact, top 47% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 3 citations in OpenAlex.

  1. Article
  2. Review
  3. Lens intermediate filaments.Experimental eye research · 2009
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 1 institution in 1 country.

Joshua T PittengerDepartment of Cell Biology and Human Anatomy, School of Medicine, University of California, Davis, CA 95616, USA.
John F Hess
Paul G Fitzgerald
University of California, Davis · US

Funding

UC Davis MCB T32 Administrative Supplement to Recognize Excellence in Diversity, Equity, Inclusion, and Accessibility (DEIA) MentorshipT32GM007377 · NIGMS · UNIVERSITY OF CALIFORNIA DAVIS · PI CHEDIN, FREDERIC LOUIS · 1985 to 2023
$9.9M
Vision Science Training Program: Cornea to CortexT32EY015387 · NEI · UNIVERSITY OF CALIFORNIA DAVIS · PI MARIE E BURNS · 2003 to 2026
$4.8M
MOLECULAR ANALYSIS OF OCULAR LENS BEADED FILAMENTSR01EY008747 · NEI · UNIVERSITY OF CALIFORNIA DAVIS · PI FITZGERALD, PAUL GILLESPIE · 1990 to 2010
$4.5M
SDSL-EPR STUDY OF INTERMEDIATE FILAMENT STRUCTURER01EY015560 · NEI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI FITZGERALD, PAUL GILLESPIE · 2006 to 2015
$3.0M
EXTRAMURAL RESEARCH FACILITIES CONSTRUCTIONC06RR012088 · NCRR · UNIVERSITY OF CALIFORNIA DAVIS · PI CURRY, FITZ-ROY E · 1996 to 1996
–
NCRR NIH HHS C06 RR012088NCRR NIH HHS C06 RR12088-01NEI NIH HHS R01 EY008747NEI NIH HHS R01 EY015560NEI NIH HHS R01 EY08747NEI NIH HHS T32 EY015387NEI NIH HHS T32 EY15387NIGMS NIH HHS T32 GM007377
6 · The paper itself

Abstract

purposePhakosin and filensin are lens fiber cell-specific intermediate filament (IF) proteins. Unlike every other cytoplasmic IF protein, they assemble into a beaded filament (BF) rather than an IF. Why the lens fiber cell requires two unique IF proteins and why and how they assemble into a structure other than an IF are unknown. In this report we test specific motifs/domains in phakosin to identify changes that that have adapted phakosin to lens-specific structure and function.

methodsPhakosin shows the highest level of sequence identity to K18, whose natural assembly partner is K8. We therefore exchanged conserved keratin motifs between phakosin and K18 to determine whether phakosin's divergent motifs could redirect the assembly of chimeric K18 and K8. Modified proteins were bacterially expressed and purified. Assembly competence was assessed by electron microscopy.

resultsSubstitution of the phakosin helix initiation motif (HIM) into K18 does not alter assembly with K8, establishing that the radical divergence in phakosin HIM is not by itself the mechanism by which IF assembly is redirected to BF assembly. Unexpectedly, K18 bearing phakosin HIM resulted in normal IF assembly, despite the presence of an otherwise disease-causing R-C substitution, and two helix-disrupting glycines. This disproves the widely held belief that mutation of the R is catastrophic to IF assembly. Additional data are presented that suggest normal IF assembly is dependent on sequence-specific interactions between the IF head domain and the HIM.

conclusionsIn the lens fiber cell, two members of the IF family have evolved to produce BFs instead of IFs, a change that presumably adapts the IF to a fiber cell-specific function. The authors establish here that the most striking divergence seen in phakosin is not, as hypothesized, the cause of this altered assembly outcome. The authors further establish that the HIM of IFs is far more tolerant of mutations, such as those that cause some corneal dystrophies and Alexander disease, than previously hypothesized and that normal assembly involves sequence-specific interactions between the head domain and the HIM.

Indexed as

Amino Acid MotifsChimerin ProteinsEye ProteinsGenetic VectorsHelix-Loop-Helix MotifsHumansIntermediate Filament ProteinsKeratin-18Lens, CrystallineMutant Chimeric ProteinsPlasmidsProtein Structure, TertiaryChimerin ProteinsEye ProteinsIntermediate Filament ProteinsKeratin-18KRT18 protein, humanMutant Chimeric Proteinsphakinin

Identifiers

PMID17962466
PMCPMC2909742
OpenAlexW2021070093

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.