# The Role of Membrane Architecture in Primary Cilium Signaling

> **NIH NIH F32** · STANFORD UNIVERSITY · 2022 · $67,582

## Abstract

Project Summary
Cilia are ubiquitous and important microtubule-based organelles involved in sensation, developmental
signaling, fluid flow and cell motility whose dysregulation leads to a range of human disease states including
cancers and ciliopathies. The non-motile primary cilium functions as a signaling antenna. It has a distinct and
tightly regulated protein and lipid composition while remaining contiguous with the plasma membrane of the
cell. Proper cilium function depends on compartmentalization both for spatial separation of ciliary activities and
high concentration of signaling components. While there has been extensive characterization of the proteins
and lipids that compose the cilium, ciliary membrane, and the diffusion barrier at its base, much less is known
about the composition and function of membrane regions proximal to the cilium that support proper signaling.
 In many cell types, the mature primary cilium sits in a microns-deep membrane invagination called the
“ciliary pocket” that is an important but under-characterized hub of endocytic activity and signaling. The
ultrastructure of the ciliary pocket is highly conserved and is distinct from both the ciliary and plasma
membranes. It has been difficult to clearly define the ciliary pocket as a distinct compartment and determine its
full contributions to ciliary signaling and function. This is in part due to the technical challenge of imaging this
diffraction limited region and lack of tools to specifically perturb the pocket’s structure and composition. In this
proposal I will address this gap through an interconnected set of aims, leveraging innovative technologies
including proximity-based labeling and super-resolution microscopy as well as functional signaling assays to:
1) define the molecular composition of the ciliary pocket, 2) determine how ciliary pocket structure is
established and maintained to support signaling, and 3) investigate extracellular roles of the ciliary pocket in
signaling. In summary, I propose to establish a high-resolution map of the architecture and spatial and
temporal dynamics of the mammalian ciliary pocket and define its role in supporting ciliary signal transduction.
 Defects in ciliary structure lead to aberrant signaling in a variety of disease states. The proposed
research will expand our understanding of how the architecture of the periciliary membrane supports proper
function of the primary cilium and has the potential to contribute new insights into the molecular basis of human
diseases such as ciliopathies and cancer.

## Key facts

- **NIH application ID:** 10394131
- **Project number:** 5F32GM142181-02
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Alexandra Fitzgerald Long
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $67,582
- **Award type:** 5
- **Project period:** 2021-04-05 → 2024-04-04

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10394131

## Citation

> US National Institutes of Health, RePORTER application 10394131, The Role of Membrane Architecture in Primary Cilium Signaling (5F32GM142181-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10394131. Licensed CC0.

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