ALAN HUETT Alan.Huett@nottingham.ac.uk
Assistant Professor
A novel hybrid yeast-human network analysis reveals an essential role for FNBP1L in antibacterial autophagy
Huett, Alan; Ng, Aylwin; Cao, Zhifang; Kuballa, Petric; Komatsu, Masaaki; Daly, Mark J.; Podolsky, Daniel K.; Xavier, Ramnik J.
Authors
Aylwin Ng
Zhifang Cao
Petric Kuballa
Masaaki Komatsu
Mark J. Daly
Daniel K. Podolsky
Ramnik J. Xavier
Abstract
Autophagy is a conserved cellular process required for the removal of defective organelles, protein aggregates, and intracellular pathogens. We used a network analysis strategy to identify novel human autophagy components based upon the yeast interactome centered on the core yeast autophagy proteins. This revealed the potential involvement of 14 novel mammalian genes in autophagy, several of which have known or predicted roles in membrane organization or dynamics. We selected one of these membrane interactors, FNBP1L (formin binding protein 1-like), an F-BAR-containing protein (also termed Toca-1), for further study based upon a predicted interaction with ATG3. We confirmed the FNBP1L/ATG3 interaction biochemically and mapped the FNBP1L domains responsible. Using a functional RNA interference approach, we determined that FNBP1L is essential for autophagy of the intracellular pathogen Salmonella enterica serovar Typhimurium and show that the autophagy process serves to restrict the growth of intracellular bacteria. However, FNBP1L appears dispensable for other forms of autophagy induced by serum starvation or rapamycin. We present a model where FNBP1L is essential for autophagy of intracellular pathogens and identify FNBP1L as a differentially used molecule in specific autophagic contexts. By using network biology to derive functional biological information, we demonstrate the utility of integrated genomics to novel molecule discovery in autophagy. Copyright © 2009 by The American Association of Immunologists, Inc.
Citation
Huett, A., Ng, A., Cao, Z., Kuballa, P., Komatsu, M., Daly, M. J., …Xavier, R. J. (2009). A novel hybrid yeast-human network analysis reveals an essential role for FNBP1L in antibacterial autophagy. Journal of Immunology, 182(8), 4917-4930. https://doi.org/10.4049/jimmunol.0803050
Journal Article Type | Article |
---|---|
Acceptance Date | Feb 4, 2009 |
Online Publication Date | Apr 2, 2009 |
Publication Date | Apr 15, 2009 |
Deposit Date | Aug 15, 2022 |
Journal | Journal of Immunology |
Print ISSN | 0022-1767 |
Electronic ISSN | 1550-6606 |
Publisher | American Association of Immunologists |
Peer Reviewed | Peer Reviewed |
Volume | 182 |
Issue | 8 |
Pages | 4917-4930 |
DOI | https://doi.org/10.4049/jimmunol.0803050 |
Public URL | https://nottingham-repository.worktribe.com/output/3181817 |
Publisher URL | https://www.jimmunol.org/content/182/8/4917 |
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