Evidence map›Paper›PMID 26029358›Full record

ArticleCilia2015

The primary cilium functions as a mechanical and calcium signaling nexus.

Kristen L Lee, Marie D Guevarra, An M Nguyen, Mardonn C Chua, Yingxiao Wang, Christopher R Jacobs

Open access · hybridAbstract read
In one paragraph

Article in Cilia, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.

0numbers the graph read from it
0cells of the map it votes in
91citing papers in PubMed
12.1field-weighted citation impact, top 1% 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

91 citing papers in PubMed, 144 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Review
  6. Review
  7. Ciliary-Mediated Mechanotransduction in Skeletal Development and Diseases.Results and problems in cell differentiation · 2026
    Review
  8. Article
  9. Review
  10. PIEZO channels as multimodal mechanotransducers.Biochemical Society transactions · 2025
    Review
  11. Article
  12. Article
  13. Measuring Calcium Signaling at the Primary Cilia.Methods in molecular biology (Clifton, N.J.) · 2025
    Article
  14. Article
  15. Review
  16. Review
  17. Article
  18. Article
  19. Article
  20. Review

31 more citing papers are in PubMed but not listed here.

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

6 authors at 2 institutions in 2 countries.

Kristen L LeeDepartment of Biomedical Engineering, Columbia University, 351 Engineering Terrace, MC 8904, 1210 Amsterdam Ave, New York, NY 10027 USA.
Marie D GuevarraDepartment of Biomedical Engineering, Columbia University, 351 Engineering Terrace, MC 8904, 1210 Amsterdam Ave, New York, NY 10027 USA.
An M NguyenDepartment of Biomedical Engineering, Columbia University, 351 Engineering Terrace, MC 8904, 1210 Amsterdam Ave, New York, NY 10027 USA ; Jacobs Technion-Cornell Innovation Institute, Cornell Tech, New York, NY 10011 USA.
Mardonn C ChuaDepartment of Biomedical Engineering, Columbia University, 351 Engineering Terrace, MC 8904, 1210 Amsterdam Ave, New York, NY 10027 USA ; Department of Biotechnology, University of British Columbia, Vancouver, BC V6T 1Z4 Canada.
Yingxiao WangBioengineering Department, UC San Diego, La Jolla, CA 92093 USA.
Christopher R JacobsDepartment of Biomedical Engineering, Columbia University, 351 Engineering Terrace, MC 8904, 1210 Amsterdam Ave, New York, NY 10027 USA.
Columbia University · USUniversity of California San Diego · US

Funding

Primary cilia as mechanotransducers in boneR01AR062177 · NIAMS · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI GUO, X. EDWARD · 2012 to 2021
$3.9M
Multidisciplinary Engineering Training in Musculoskeletal ResearchT32AR059038 · NIAMS · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI ATESHIAN, GERARD A. · 2011 to 2015
$1.3M
NIAMS NIH HHS R01 AR062177NIAMS NIH HHS T32 AR059038
6 · The paper itself

Abstract

backgroundThe primary cilium is an antenna-like, nonmotile structure that extends from the surface of most mammalian cell types and is critical for chemosensing and mechanosensing in a variety of tissues including cartilage, bone, and kidney. Flow-induced intracellular calcium ion (Ca(2+)) increases in kidney epithelia depend on primary cilia and primary cilium-localized Ca(2+)-permeable channels polycystin-2 (PC2) and transient receptor potential vanilloid 4 (TRPV4). While primary cilia have been implicated in osteocyte mechanotransduction, the molecular mechanism that mediates this process is not fully understood. We directed a fluorescence resonance energy transfer (FRET)-based Ca(2+) biosensor to the cilium by fusing the biosensor sequence to the sequence of the primary cilium-specific protein Arl13b. Using this tool, we investigated the role of several Ca(2+)-permeable channels that may mediate flow-induced Ca(2+) entry: PC2, TRPV4, and PIEZO1.

resultsHere, we report the first measurements of Ca(2+) signaling within osteocyte primary cilia using a FRET-based biosensor fused to ARL13B. We show that fluid flow induces Ca(2+) increases in osteocyte primary cilia which depend on both intracellular Ca(2+) release and extracellular Ca(2+) entry. Using siRNA-mediated knockdowns, we demonstrate that TRPV4, but not PC2 or PIEZO1, mediates flow-induced ciliary Ca(2+) increases and loading-induced Cox-2 mRNA increases, an osteogenic response.

conclusionsIn this study, we show that the primary cilium forms a Ca(2+) microdomain dependent on Ca(2+) entry through TRPV4. These results demonstrate that the mechanism of mechanotransduction mediated by primary cilia varies in different tissue contexts. Additionally, we anticipate that this work is a starting point for more studies investigating the role of TRPV4 in mechanotransduction.

Indexed as

BiosensorCalcium signalingKidney epitheliaMechanotransductionOsteocytePrimary cilium

Identifiers

PMID26029358
PMCPMC4448211
OpenAlexW1491831470

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.