# Cell adhesion mediated by LINKIN

> **NIH NIH R01** · CALIFORNIA INSTITUTE OF TECHNOLOGY · 2020 · $373,501

## Abstract

Project Summary
Cell adhesion is crucial aspect of development, fertilization, tissue homeostasis, protection from and interaction
with other organisms. Many adhesion proteins have been intensively studied for decades and it was an open
question whether we have sufficient knowledge of adhesion, given the large number of interacting proteins and
interactions involved in adhesion. LINKIN is a conserved, transmembrane protein that we found to be involved
in cell adhesion, suggesting that by studying LINKIN and its interacting proteins we can define a new cellular
pathway involved in cell adhesion. The striking conservation of LINKIN sequence and gene copy number
across eukaryotic evolution suggests a critical role in development. We discovered LINKIN's role in cell
adhesion in the context of C. elegans development, specifically the attachment of the migrating linker cell to
the vas deferens, which provides a powerful assay for its structure, function and interactions. We identified
interacting proteins in human cells and provided evidence for similar molecular interactions in both organisms.
We identified the RUVBL1 and RUVBL2 AAA-ATPases, and α-tubulin as cytoplasmic interactors of LINKIN,
suggesting a role for LINKIN in regulating microtubule dynamics, but further investigation is required to connect
LINKIN to other interactors and signaling pathways. We propose to further characterize LINKIN's role in cell
adhesion in order to connect this new adhesion molecule to other known (or unknown) cellular pathways. A
major limitation of human genetic, genomic and systems biology approach is our understanding of the function
of many genes. By discovering a new pathway, we will increase the likelihood that genomic, clinical and
genetic studies will be interpretable. We will analyze the function and interactors of both the extracellular and
intracellular domains of LINKIN. Using evolutionary conservation as a guide we will mutate conserved residues
in C. elegans LINKIN and test their function in transgenic worms. We will use human LINKIN proteins with
cognate mutations in cell lines for immunoprecipitation and quantitative mass spectrometry proteomics to
identify physiologically relevant interacting proteins. We will test the function of interacting proteins identified by
the proteomics in C. elegans and cell lines. We will also use C. elegans genetics to screen prioritized
candidates for a role in adhesion using the linker cell attachment assay. Candidates will be prioritized by
expression in the linker cell, for which we have a deep transcriptomic profile, predictions of encoding
transmembrane or secreted proteins, phylogenetic co-occurrence as well as network predictions of interactions
based on orthologous proteins in other intensively-studied organisms. In this way, we will identify the portions
of LINKIN that are crucial to its function in adhesion and physiologically-relevant interacting proteins both on
other cells and same cell that likely mediate ...

## Key facts

- **NIH application ID:** 9938586
- **Project number:** 5R01HD086596-05
- **Recipient organization:** CALIFORNIA INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Tsui-Fen Chou
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $373,501
- **Award type:** 5
- **Project period:** 2016-09-20 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9938586

## Citation

> US National Institutes of Health, RePORTER application 9938586, Cell adhesion mediated by LINKIN (5R01HD086596-05). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9938586. Licensed CC0.

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