# Regulated exocytosis of lysosomes and plasma membrane repair

> **NIH NIH R01** · UNIV OF MARYLAND, COLLEGE PARK · 2020 · $451,310

## Abstract

Summary
The rapid resealing of plasma membrane wounds is critical for cellular survival. Work supported by previous
cycles of this grant showed that plasma membrane repair involves Ca2+-triggered exocytosis of lysosomes
followed by massive endocytosis. Injury-induced release of lysosomal acid sphingomyelinase triggers a
cholesterol/sphingolipid-dependent, clathrin-independent form of endocytosis, which involves caveolae or
tubular invaginations that pinch off from the plasma membrane and carry lesions into cells for degradation.
Clathrin-independent endocytosis has been described in many cell types, but there is considerable debate
about how many independent pathways exist, and how they are initiated. By demonstrating that plasma
membrane injury, Ca2+ influx and secretion of lysosomal acid sphingomyelinase trigger clathrin-independent
endocytosis, our results have introduced much needed clarity to this field. The studies we now propose provide
a unique opportunity for understanding how clathrin-independent endocytosis is regulated by plasma
membrane injury, and how it promotes wound removal. Strikingly, our recent studies in B lymphocytes suggest
that endocytosis-dependent plasma membrane repair and BCR-mediated B cell activation interfere with each
other because of competition for lipid rafts, the cholesterol/sphingolipid-enriched plasma membrane
microdomains that play a central role in clathrin-independent endocytosis and in BCR signaling and
internalization after antigen capture. To understand the physiological impact of these findings, we will pursue
two specific aims: 1) Characterize the injury-induced clathrin-independent form of endocytosis that promotes
plasma membrane repair; 2) Examine the impact of plasma membrane wounding and repair on the regulation
of B cell activation. These studies will significantly advance our understanding of clathrin-independent
endocytosis and its role in plasma membrane resealing, and demonstrate how plasma membrane injury and
repair regulate the function of B lymphocytes, cells that play an essential role in immune protection against
infectious agents.

## Key facts

- **NIH application ID:** 9936164
- **Project number:** 5R01GM064625-16
- **Recipient organization:** UNIV OF MARYLAND, COLLEGE PARK
- **Principal Investigator:** Norma Windsor Andrews
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $451,310
- **Award type:** 5
- **Project period:** 2002-08-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9936164

## Citation

> US National Institutes of Health, RePORTER application 9936164, Regulated exocytosis of lysosomes and plasma membrane repair (5R01GM064625-16). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9936164. Licensed CC0.

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