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Peer-reviewedCC BYJournal of cardiovascular development and disease

BRD10 Regulates DZIP1 Localization at the Primary Cilium During Mitral Valvulogenesis.

  • Brian Loizzi1
  • Lilong Guo1,2
  • Matthew Huff1
  • Prakrit Subba1
  • Magdalena K Brei1
  • Ranan Phookan1
  • Roman Fenner1
  • Kathryn Byerly1
  • Baylee Westbury1
  • Sarah Dooley1
  • Russell A Norris1,3
  1. 1Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29407, USA.
  2. 2Department of Pathology, Medical University of South Carolina, Charleston, SC 29407, USA.
  3. 3Department of Neurosurgery, Medical University of South Carolina, Charleston, SC 29407, USA.
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Abstract

Mitral valve prolapse (MVP) is a common congenital valve disorder that has been linked to defects in primary cilia during cardiac development, yet the mechanisms connecting ciliary regulation to valvulogenesis remain incompletely understood. As DZIP1 is required for ciliogenesis and has been shown to be involved in MVP pathogenesis, we sought to identify interacting partners that may regulate its localization and function. Using an unbiased yeast two-hybrid screen of a human heart cDNA library, we identified BRD10, a previously uncharacterized bromodomain-containing protein, as a DZIP1-interacting partner. Co-immunoprecipitation confirmed the DZIP1-BRD10 interaction and mapped the binding region to a conserved domain containing a putative nuclear localization sequence. RNAscope and immunofluorescence demonstrated that BRD10 and DZIP1 are co-expressed in developing murine valve cells, with BRD10 localizing near the basal body and transition zone of the primary cilium. BRD10 also interacted with acetylated α-tubulin, supporting a relationship with ciliary microtubule structures. Nuclear-cytoplasmic fractionation further showed that BRD10 promotes cytoplasmic enrichment of DZIP1. Together, these findings identify BRD10 as a novel regulator of DZIP1 subcellular localization and suggest that bromodomain-mediated recruitment at the primary cilium may contribute to normal valvulogenesis and developmental mechanisms relevant to MVP.

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Cite

BibTeXRIS
BibTeX
@article{loizzi2026brd10,
  title = {{BRD10 Regulates DZIP1 Localization at the Primary Cilium During Mitral Valvulogenesis.}},
  author = {Brian Loizzi and Lilong Guo and Matthew Huff and Prakrit Subba and Magdalena K Brei and Ranan Phookan and Roman Fenner and Kathryn Byerly and Baylee Westbury and Sarah Dooley and Russell A Norris},
  journal = {Journal of cardiovascular development and disease},
  year = {2026},
  month = oct,
  doi = {10.3390/jcdd13100516},
  url = {https://europepmc.org/article/MED/42930912},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - BRD10 Regulates DZIP1 Localization at the Primary Cilium During Mitral Valvulogenesis.
AU  - Brian Loizzi
AU  - Lilong Guo
AU  - Matthew Huff
AU  - Prakrit Subba
AU  - Magdalena K Brei
AU  - Ranan Phookan
AU  - Roman Fenner
AU  - Kathryn Byerly
AU  - Baylee Westbury
AU  - Sarah Dooley
AU  - Russell A Norris
PY  - 2026
DA  - 2026/10/14
JO  - Journal of cardiovascular development and disease
DO  - 10.3390/jcdd13100516
UR  - https://europepmc.org/article/MED/42930912
AB  - Mitral valve prolapse (MVP) is a common congenital valve disorder that has been linked to defects in primary cilia during cardiac development, yet the mechanisms connecting ciliary regulation to valvulogenesis remain incompletely understood. As DZIP1 is required for ciliogenesis and has been shown to be involved in MVP pathogenesis, we sought to identify interacting partners that may regulate its localization and function. Using an unbiased yeast two-hybrid screen of a human heart cDNA library, we identified BRD10, a previously uncharacterized bromodomain-containing protein, as a DZIP1-interacting partner. Co-immunoprecipitation confirmed the DZIP1-BRD10 interaction and mapped the binding region to a conserved domain containing a putative nuclear localization sequence. RNAscope and immunofluorescence demonstrated that BRD10 and DZIP1 are co-expressed in developing murine valve cells, with BRD10 localizing near the basal body and transition zone of the primary cilium. BRD10 also interacted with acetylated α-tubulin, supporting a relationship with ciliary microtubule structures. Nuclear-cytoplasmic fractionation further showed that BRD10 promotes cytoplasmic enrichment of DZIP1. Together, these findings identify BRD10 as a novel regulator of DZIP1 subcellular localization and suggest that bromodomain-mediated recruitment at the primary cilium may contribute to normal valvulogenesis and developmental mechanisms relevant to MVP.
SN  - 2308-3425
ER  -