# L1CAM adhesion and signaling pathways in C. elegans

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2021 · $328,308

## Abstract

PROJECT SUMMARY/ABSTRACT
 L1CAMs are a family of immunoglobulin cell adhesion molecules that play important roles in the
development of nervous system, including axon guidance and morphogenesis as well as axon
myelination. Mutations in L1CAMs are directly linked to the neurological L1 syndrome, the symptoms of
which include mental retardation and hydrocephalus. In addition, L1CAMs are implicated in
neurosychiatric disorders, including schizophrenia, the autistic spectrum disorder, and addiction. One
salient feature of L1CAM-associated diseases is that they are heterogeneous and genetically complex
and subject to genetic modification, pointing to the existence of as-yet-unidentified functions for L1CAMs
that are likely masked by genetic compensatory mechanisms. As transmembrane proteins, L1CAMs sit
on the plasma membrane and thus are primed to integrate extracellular signals, converting them into
cellular responses that require cross-talk with the cytoskeletal and intracellular signaling networks.
Molecular mechanisms by which cell adhesion receptors relay these signals are just beginning to be
uncovered, but much is still unknown. This application seeks to fill these gaps, identifying previously-
uncharacterized L1CAM functions in synaptic regulation and defining the molecular mechanisms by
which L1CAMs are functionally linked to intracellular signaling networks.
 We have established C. elegans as a powerful genetic system to dissect the roles and
mechanisms of L1CAMs. In our previous studies, we determined that the C. elegans L1CAMs, SAX-7
LAD-2 function in maintaining nervous system integrity and axon guidance respectively. We have made
significant inroads into defining L1CAM mechanisms of action that are remarkably conserved between
mammals and C. elegans. Our recent studies, which took advantage of the ability to easily conduct
modifier screens in C. elegans, identified the interplay between the mitogen-activated protein kinase
(MAPK) signaling cascade and L1CAMs in an unexpected role in synaptic regulation. To better define
the molecular mechanisms that link L1CAMs and MAPK to the synaptic machinery, our aims are 1) to
define the roles of SAX-7 and MAPK in the synaptic vesicle cycle, 2) to resolve how SAX-7 and MAPK-1
coordinately regulate synaptic function, and 3) to define the factors that mediate SAX-7 and MAPK roles
in synaptic transmission. With L1CAMs and MAPK implicated in both intellectual disability and the
autism spectrum, this basic research in C. elegans will reveal fundamental knowledge on synaptic
modulation that will provide additional insight into mechanisms underlying human neuropsychiatric
disorders.

## Key facts

- **NIH application ID:** 10087972
- **Project number:** 5R01NS045873-13
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** LIHSIA CHEN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $328,308
- **Award type:** 5
- **Project period:** 2005-02-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10087972

## Citation

> US National Institutes of Health, RePORTER application 10087972, L1CAM adhesion and signaling pathways in C. elegans (5R01NS045873-13). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10087972. Licensed CC0.

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