# PATTERN GENERATION OF ACTIN FILAMENTS

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 1994 · $247,535

## Abstract

Actin filaments are key elements in the dynamic machinery of motile cells
and in the scaffolding that maintains the shape of cells. Three cell types,
each of which is specialized in such a way that separate characteristics of
the actin cytoskeleton and its regulation will be studied. 1) The acrosomal
reaction of Thyone sperm as a model system for investigations of the
polymerization of actin. For example, how is the unpolymerized actin
maintained in an insoluble state prior to induction and what role, if any,
do precursor phospholipids, more specifically, phosphoinositol, play in
regulation actin assembly? 2) The differentiation of hair cells of the
chicken cochlea as a model for understanding how the length, number, and
distribution of actin filaments is determined. First, is the length of the
actin filaments regulated by capping macromolecules? This could be
determined by adding exogenous gel filtered monomeric actin to detergent
extracted sensory epithelia under polymerizing conditions. Those filaments
that are capped should fail to elongate, while those that are uncapped will
elongate. Second, when in development are new filaments added to the
existing stereociliary actin bundle and where does nucleation occur? Third,
how is the cuticular plate, a naturally occurring actin gel, formed? In
collaboration with David DeRosier we will look at what proteins are
involved and how they produce this gel. Fourth, how do actin binding
proteins specifically "know" where to bind, e.g. to the stereocilia, the
cuticular plate, or zonula adhaerens ring? Fifth, using in situ
hybridization techniques it would be interesting to try to determine when
the mRNA for actin is made in differentiating, hair cells and how different
hair cells end up with the same amount of F-actin. 3) The growth and spread
of the intracytoplasmic bacterial parasite, Listeria, as a model for
identifying substances that nucleate the polymerization of actin and
control the length of actin filaments. These studies are also of importance
medically as we are studying the cell biology of entry, reproduction, and
spread in host macrophages. Listeria is a model for other even more
virulent bacterial such as Shigella. First, I will examine actin nucleation
from the surface of Listeria by adding exogenous gel filtered actin to
detergent extracted infected macrophages to see if Listeria will induce
actin assembly from its surface. Second, in collaboration with Dan Portnoy,
we will isolate mutant strains of Listeria that do not spread from cell to
cell because they lack associated actin filaments. From these mutants I
hope to identify the gene and gene products in Listeria that are needed for
actin nucleation.

## Key facts

- **NIH application ID:** 2197100
- **Project number:** 5R01HD014474-15
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **SAM.gov UEI:** GM1XX56LEP58
- **Principal Investigator:** LEWIS G TILNEY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $247,535
- **Award type:** 5
- **Project period:** 1980-07-01 → 1995-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2197100

## Citation

> US National Institutes of Health, RePORTER application 2197100, PATTERN GENERATION OF ACTIN FILAMENTS (5R01HD014474-15). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/2197100. Licensed CC0.

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