# Molecular basis for BMP receptor specialization and trafficking

> **NIH NIH F32** · UNIVERSITY OF PENNSYLVANIA · 2024 · $69,080

## Abstract

PROJECT SUMMARY
Bone morphogenetic protein (BMP) signaling, as part of the TGF-beta signaling family, is a major
driver of developmental processes. Mutations in genes encoding BMP pathway components are
associated with cardiovascular, pulmonary, and skeletal diseases as well as cancer.
Developmentally, BMPs serve as morphogens, with slight changes in signal level resulting in distinct
cell fates. For instance, during dorsoventral axial patterning, the BMP gradient patterns the axial
tissue with high BMP levels instructing ventral cell fates. Precise regulation of the BMP morphogen
gradient is required for proper signaling and patterning, though has mostly focused on how ligand
concentration and activity impact biological outcomes. Our lab has recently shown that during
dorsoventral patterning, there are two required Type I BMP receptors, Acvr1l and Bmpr1a; however,
only the kinase activity of Acvr1l is required for signaling. The specific requirement of Bmpr1a has not
been identified, nor have the distinct requirements for Type II receptors. Prior work in other systems
has also demonstrated that trafficking of TGF-beta receptors can attenuate or dampen signal
transduction, representing another mechanism by which receptor activity can alter BMP signaling.
Mutations in BMP receptors are associated with cancer and, specifically, mutations in Acvr1 are
associated with brain gliomas and the developmental disorder fibrodysplasia ossificans progressiva,
though how these mutations impact BMP signaling levels and lead to disease are still being defined.
Here, I propose to determine the molecular basis for BMP receptor specialization and trafficking using
zebrafish dorsoventral axial patterning as a model. I hypothesize that the BMP signaling gradient is
interpreted by specialized receptor functions and trafficking to fine tune signal transduction
downstream of ligand concentration. Building upon recent evidence that Type I BMP receptors have
specialized roles in the zebrafish gastrula, I will directly test the capacity for each Type I receptor to
be activated by Type II receptors and, therefore, perform its kinase function. I will also determine non-
kinase based requirements for Bmpr1a in forming the receptor complex. Finally, I will define
mechanisms of receptor trafficking in the gastrula, characterizing where and through which pathways
receptors are trafficked to and from the cell membrane. I will then functionally test the requirements
for trafficking on BMP signaling levels and dorsoventral patterning by disrupting trafficking pathways.
Together, these studies will elucidate specialized requirements for BMP receptors in signal
transduction.

## Key facts

- **NIH application ID:** 10826045
- **Project number:** 1F32HD114468-01
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Jeet H Patel
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $69,080
- **Award type:** 1
- **Project period:** 2024-04-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10826045

## Citation

> US National Institutes of Health, RePORTER application 10826045, Molecular basis for BMP receptor specialization and trafficking (1F32HD114468-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10826045. Licensed CC0.

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