# The relationship between Rab11-endosomes and the centrosome during division

> **NIH NIH R01** · SYRACUSE UNIVERSITY · 2020 · $315,000

## Abstract

SUMMARY STATEMENT: Ciliopathies comprise a group of disorders associated with genetic
mutations encoding defective proteins, which result in either abnormal formation or function of cilia.
Ciliopathies have been linked to defects in molecular pathways organized at the primary cilium's basal
body/centrosome and the primary cilium itself. Patients suffering from ciliopathies can display defects in
left/right asymmetry, congenital cardiac defects, and formation of cysts in multiple organs including
liver, pancreas and kidney. In vertebrates, motile cilia located in an organ of asymmetry play an
important role in left-right development. Evidence from model organisms, such as zebrafish organ of
asymmetry (Kupffer's Vesicle, KV), indicates that conserved cilia-driven left-right flow establishes left-
right signals to regulate target genes to control left/right asymmetry. This project addresses the
question: How do ciliated cells develop into a functional polarized organ? We propose this occurs
through a sequential process that starts with cell division, polarity formation, and finishes with cilia
assembly. If a ciliated organ wants to expand its central lumen, cells need to re-enter the cell cycle and
correctly position its mitotic spindle along the longest axis parallel to the expanding lumen. We found
that both Rab11-associated endosomes and a centrosome protein, cenexin, regulate the positioning of
the mitotic spindle and ciliogenesis (Hehnly and Doxsey, 2014; Hung et al., 2016), but whether they act
together during these processes has not been examined. During interphase, Rab11-endosomes
associate with mother centriole sub-distal appendages where cenexin resides (Hehnly et al., 2012).
Rab11 and a second GTPase, Rab8, can directly interact with cenexin. In addition, a GTPase cascade
has been identified between Rab11 and Rab8 during ciliogenesis and apical membrane initiation, but if
it requires the centrosome or occurs during specific points of the cell cycle is unknown. We will test the
overall hypothesis that anchoring Rab11 and/or Rab8 by the mother centriole appendage protein,
cenexin, is required for spindle positioning, polarity formation and/or ciliogenesis. To test this we will
determine whether the centrosome can modulate Rab11 and/or Rab8 activity (Aim 1) and determine
when during the cell cycle Rab11 and Rab8 activity is required to regulate tissue morphogenesis (Aim
2). This will be accomplished by using a 3-D kidney epithelial cell culture model and an in vivo
developmental model, zebrafish KV formation, to identify a framework for how polarity formation relates
to the cell cycle.!

## Key facts

- **NIH application ID:** 9953827
- **Project number:** 5R01GM127621-04
- **Recipient organization:** SYRACUSE UNIVERSITY
- **Principal Investigator:** Heidi Hehnly
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $315,000
- **Award type:** 5
- **Project period:** 2018-07-03 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9953827

## Citation

> US National Institutes of Health, RePORTER application 9953827, The relationship between Rab11-endosomes and the centrosome during division (5R01GM127621-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9953827. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*