# F-BAR proteins in neuronal migration and process formation

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2021 · $388,750

## Abstract

Breaking neuronal symmetry is a fundamental process in the formation of a polarized neuron. Neurons in the
developing cerebral cortex are born as spherical cells that must extend leading and trailing processes to migrate
to their destination in the developing cortical plate. Cortical neurons then extend long axons and dendrites from
these processes to create functional circuits. Cortical neuron migration and process extension is critically
dependent on the microtubule and actin cytoskeleton, but relatively little is known about how the actin cytoskeleton
and plasma membrane are coordinated during these events. Membrane protrusion and invagination are
fundamental cellular activities that require coordination of the plasma membrane and underlying actin cytoskeleton.
However, there is a dearth of data on how membrane protrusion and invagination are integrated in process
outgrowth and neuronal migration. The F-BAR superfamily of proteins are involved in membrane curvature sensing
and deformation through their F-BAR domain, positioning them as potentially important players in both membrane
invagination and protrusion. Structurally, they form a curved dimer that self-multimerizes around endocytic
vesicles, causing their elongation into tubules. The CIP4 family of proteins (CIP4, FBP17 and TOCA1) is a group
of F-BAR proteins that bind actin-associated proteins. Like other F-BAR proteins, the CIP4 family is thought to
function primarily in membrane invagination and endocytosis, but our recent work has implicated CIP4 in neuronal
membrane protrusion as well. Lamellipodial-like protrusions induced by CIP4 strongly inhibit neurite outgrowth in
culture. Conversely, we find that a close family member, FBP17, forms endocytic tubules in developing cortical
neurons and promotes prominent filopodia formation, resulting in precocious neurite outgrowth. In this proposal we
will test the novel hypothesis that protrusion through CIP4 and invagination through FBP17 act in opposing
manners to regulate cortical neuron migration and process formation in the developing cortex. Specifically, we will:
1) Determine how CIP4 induces membrane protrusions and FBP17 forms endocytic tubules, 2) Establish how
membrane tubulation results in precocious filopodia formation and neurite outgrowth, 3) Reveal the spatial and
temporal expression pattern of endogenously-labeled CIP4 and FBP17 in mouse lines and 4) Resolve CIP4 and
FBP17 function in cortical development in vivo. This work will provide fundamental insights into how proteins that
bridge the membrane and actin cytoskeleton function to regulate process outgrowth and cortical neuron migration
in the early developing mammalian brain. CIP4 and FBP17 have been implicated in Huntington's disease and
several forms of cancer, underscoring the importance of determining the function of these proteins in the developing
cerebral cortex.

## Key facts

- **NIH application ID:** 10317364
- **Project number:** 1R01NS115400-01A1
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Erik W Dent
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $388,750
- **Award type:** 1
- **Project period:** 2021-08-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10317364

## Citation

> US National Institutes of Health, RePORTER application 10317364, F-BAR proteins in neuronal migration and process formation (1R01NS115400-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10317364. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*