The Drosophila gene encoding JIG protein (CG14850) is critical for CrebA nuclear trafficking during development
Abstract
Coordination of mitochondrial and nuclear processes is key to the cellular health; however, very little is known about the molecular mechanisms regulating nuclear-mitochondrial crosstalk. Here, we report a novel molecular mechanism controlling the shuttling of CREB (cAMP response element-binding protein) protein complex between mitochondria and nucleoplasm. We show that a previously unknown protein, herein termed as Jig, functions as a tissue-specific and developmental timing-specific coregulator in the CREB pathway. Our results demonstrate that Jig shuttles between mitochondria and nucleoplasm, interacts with CrebA protein and controls its delivery to the nucleus, thus triggering CREB-dependent transcription in nuclear chromatin and mitochondria. Ablating the expression of Jig prevents CrebA from localizing to the nucleoplasm, affecting mitochondrial functioning and morphology and leads to Drosophila developmental arrest at the early third instar larval stage. Together, these results implicate Jig as an essential mediator of nuclear and mitochondrial processes. We also found that Jig belongs to a family of nine similar proteins, each of which has its own tissue- and time-specific expression profile. Thus, our results are the first to describe the molecular mechanism regulating nuclear and mitochondrial processes in a tissue- and time-specific manner.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- May 05, 2023
- Source ID
- 10.1093/nar/gkad343
Entities
People
- Alexei Tulin
- Gbolahan Bamgbose
- Guillaume Bordet
- Sayem H Bhuiyan
Organizations
- National Institutes of Health
- National Science Foundation
- United States Department of Defense
- University of North Dakota