Biology subjects

Kornberg, T.

Publications and source records attributed to Kornberg, T..

4 recordsLinked to original sources

bioRxiv2026

Heparan sulfate is essential for Drosophila FGF export

Binding of Fibroblast growth factor (FGF) to a heparan sulfate proteoglycan (HSPG) is required for paracrine FGF signaling. To improve our understanding of FGF:HSPG association, we developed a method to monitor export of the Drosophila FGF ortholog Branchless (Bnl) in vivo. We detected Bnl on the surface of approximately 10% of Bnl-producing cells, but Bnl on the surface of cells depleted of HS was much reduced. HS depletion also non-autonomously decreased the activity of cytonemes that extend from cells that receive Bnl. These results are consistent with the idea that Bnl export to the cell surface is regulated, that intracellular binding of an HSPG to Bnl in producing cells is essential for export, and that cells that take up Bnl actively participate in its release from producing cells. SummaryLevels of FGF exported to the surface of FGF-expressing cells are dependent on intracellular heparan sulfate proteoglycans.

developmental biology↗

bioRxiv2026

Smoothened turnover regulated by Hedgehog signaling in Drosophila

During development, the processes of cell-cell signaling orchestrate growth and morphogenesis using both static features and moving parts. For example, expression domains of genes which set states of determination may be fixed in space for periods of time, but multiple signals move between the determined cells and intracellular movements of components of the signal transduction machines are key to information exchange. In the Drosophila wing imaginal disc, Hedgehog (Hh) protein produced in the posterior compartment moves to cells across the anterior/posterior compartment border to induce signal transduction and various intracellular responses. In this work, we investigated protein turnover and intracellular trafficking of components of Hh signal transduction in the wing disc and found that both are major features of Hh signaling. SummaryThe intracellular distribution and half-life of Smoothened is regulated by Hedgehog signaling.

developmental biology↗

bioRxiv2020

The conserved ER-transmembrane protein TMEM39 coordinates with vesicular COPII to promote collagen secretion and prevent ER stress

Dysregulation of collagen production and secretion contributes to aging and tissue fibrosis of major organs. How premature collagen proteins in the endoplasmic reticulum (ER) route as specialized cargos for secretion remains to be fully elucidated. Here, we report that TMEM39, an ER-localized transmembrane protein, regulates production and secretory cargo trafficking of procollagen. We identify the C. elegans ortholog TMEM-39 from an unbiased RNAi screen and show that deficiency of tmem-39 leads to striking defects in cuticle collagen production and constitutively high ER stress response. RNAi knockdown of the tmem-39 ortholog in Drosophila causes similar defects in collagen secretion from fat body cells. The cytosolic domain of human TMEM39A binds to Sec23A, a vesicle coat protein that drives collagen secretion and vesicular trafficking. TMEM-39 regulation of collagen secretion is independent of ER stress response and autophagy. We propose that roles of TMEM-39 in collagen secretion and preventing ER stress are likely evolutionarily conserved.

cell biology↗

bioRxiv2019

Broadly Conserved Roles of TMEM-131 Family Proteins in Intracellular Collagen Assembly and Secretory Cargo Trafficking

Collagen is the most abundant protein in animals. Its dysregulation contributes to ageing and human disorders including tissue fibrosis in major organs. How premature collagens in the endoplasmic reticulum (ER) assemble and route for secretion remains molecularly undefined. From an RNAi screen, we identified an uncharacterized C. elegans gene tmem-131, deficiency of which impairs collagen production and activates ER stress response. TMEM-131 N-termini contain bacterial PapD chaperone-like (PapD-L) domains essential for collagen assembly and secretion. Human TMEM131 binds to COL1A2 and TRAPPC8 via N-terminal PapD-L and C-terminal domain, respectively, to drive collagen production. We provide evidence that previously undescribed roles of TMEM131 in collagen recruitment and secretion are evolutionarily conserved in C. elegans, Drosophila and humans.

cell biology↗