# The Regulation of Macropinocytosis

> **NIH NIH R35** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $458,744

## Abstract

Abstract:
Macropinosomes are relatively large endocytic vesicles which form in nearly all growing
metazoan cells by movements of plasma membrane and the actin cytoskeleton, and which
deliver extracellular solutes into lysosomes by microtubule-dependent membrane fusion
reactions. Macropinocytosis is the route by which many pathogenic bacteria and viruses invade
host cells, antigen is sampled for initiation of immune responses, and extracellular nutrients are
ingested to support the growth of K-Ras-transformed cancer cells. Research in the Swanson lab
has introduced foundational concepts about macropinocytosis, including how membrane
phospholipid-modifying enzymes and cytoskeletal activities coordinate macropinosome
formation, how macropinosomes transmit growth signals from cell surface receptors to the
mechanistic target of rapamycin complex-1 (mTORC1) on lysosomal membranes, and how
macropinocytosis limits damage to lysosomal membranes in activated macrophages. Despite
the recognized importance of macropinocytosis in health and disease, and the considerable
progress in understanding its mechanism and regulation, significant questions remain
unanswered: (1) How does type 1 phosphatidylinositol 3-kinase organize macropinocytic cup
closure into macropinosomes? (2) How do Src-family kinases regulate macropinocytosis? (3)
What molecules or activities determine whether macropinosomes deliver their solute contents
into lysosomes or recycle them to the cell surface? (4) How does cellular nutrient status
influence solute accumulation by macropinocytosis? This research program uses innovative
approaches to cell biology, molecular genetics and quantitative microscopy to answer these
fundamental questions. The continuation of this research will put macropinocytosis into the
context of cell growth, metabolism and innate immunity, and could lead to new therapeutic
approaches to cancer, infectious diseases and disorders of the immune system.

## Key facts

- **NIH application ID:** 9893006
- **Project number:** 5R35GM131720-02
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** JOEL A SWANSON
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $458,744
- **Award type:** 5
- **Project period:** 2019-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9893006

## Citation

> US National Institutes of Health, RePORTER application 9893006, The Regulation of Macropinocytosis (5R35GM131720-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9893006. Licensed CC0.

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