# CYTOSKELETON AND PLATELET CLEARANCE

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2021 · $396,250

## Abstract

Platelets, harvested for transfusion, have a relatively short “shelf life” of 5 days. With increasing storage, platelets
develop structural and functional changes called “platelet storage lesions”. These changes result not only in
reduced hemostatic response to agonists but also in an accelerated clearance from the circulation in vivo.
Several mechanisms have been proposed including clustering of the platelet glycoprotein Ib complex on the
surface of platelets, alterations in glycans leading to recognition by hepatic Ashwell-Morell receptor and shedding
of platelet glycoprotein Ibα. Exposure of phosphatidylserine (PS) on stored platelet surface is a well known tag
for clearance from the circulation. In resting platelets, PS is located in the inner leaflet of the membrane bilayer
and there is transbilayer movement from the inner to the outer leaflet during storage and during platelet
activation. Both a senescence (or apoptosis)- induced and an activation-dependent pathways of PS exposure
have been described. Exposure of PS in senescent platelets occurs through the mitochondrial Bcl-2 family of
proteins and (in contrast to activation-induced PS exposure) it does not require elevation of cytosolic Ca+ and it
involves cytochrome c release and subsequent activation of caspase 3. PS exposure occurs simultaneously
with the generation of microparticles and stored platelet preparation contain PS-rich microparticles. The
molecular mechanisms that maintain the phospholipid asymmetry in resting platelets, as in most mammalian
cells, are not known. We propose a novel mechanism for the loss of phospholipid asymmetry during storage.
We posit that the cortical actin network confines PS to the inner leaflet and hypothesize that during storage the
reorganization of cytoskeleton releases normal constraints on plasma membrane bilayer leading to the loss of
asymmetry and transbilayer movement of anionic phospholipids. The cytoskeletal proteins, tightly bound to
anionic phospholipids such as actin, are also exteriorized to the cytoplasmic surface possibly with a putative
scramblase-dependent mechanism. The overall objective of the grant is to delineate the mechanisms that
maintain phospholipid asymmetry in fresh platelets and its loss during storage. Specific aims of this proposal
are: The specific aims of the proposal are (1) to determine the role of the cortical actin network in
maintaining the phospholipid asymmetry, (2) to define the mechanism of regulation of cofilin-1-induced
PS exposure in stored platelets and (3) to determine the effect of cofilin-1 inhibition on platelet survival.

## Key facts

- **NIH application ID:** 10167760
- **Project number:** 5R01HL139501-04
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Perumal Thiagarajan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $396,250
- **Award type:** 5
- **Project period:** 2018-08-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10167760

## Citation

> US National Institutes of Health, RePORTER application 10167760, CYTOSKELETON AND PLATELET CLEARANCE (5R01HL139501-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10167760. Licensed CC0.

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