A novel hybrid yeast-human network analysis reveals an essential role for FNBP1L in antibacterial autophagy

Alan Huett, Aylwin Ng, Zhifang Cao, Petric Kuballa, Masaaki Komatsu, Mark J. Daly, Daniel K. Podolsky, Ramnik J. Xavier

Research output: Contribution to journalArticle

40 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)4917-4930
Number of pages14
JournalJournal of Immunology
Volume182
Issue number8
DOIs
StatePublished - Apr 15 2009

Fingerprint

Autophagy
Carrier Proteins
Yeasts
Salmonella enterica
Fungal Proteins
Membranes
Sirolimus
Starvation
Genomics
RNA Interference
Organelles
Bacteria
Growth
Serum

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

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

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.

In: Journal of Immunology, Vol. 182, No. 8, 15.04.2009, p. 4917-4930.

Research output: Contribution to journalArticle

Huett, Alan ; Ng, Aylwin ; Cao, Zhifang ; Kuballa, Petric ; Komatsu, Masaaki ; Daly, Mark J. ; Podolsky, Daniel K. ; Xavier, Ramnik J. / A novel hybrid yeast-human network analysis reveals an essential role for FNBP1L in antibacterial autophagy. In: Journal of Immunology. 2009 ; Vol. 182, No. 8. pp. 4917-4930.
@article{712a77080c454137beaa28a22a33ccb2,
title = "A novel hybrid yeast-human network analysis reveals an essential role for FNBP1L in antibacterial autophagy",
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.",
author = "Alan Huett and Aylwin Ng and Zhifang Cao and Petric Kuballa and Masaaki Komatsu and Daly, {Mark J.} and Podolsky, {Daniel K.} and Xavier, {Ramnik J.}",
year = "2009",
month = "4",
day = "15",
doi = "10.4049/jimmunol.0803050",
language = "English (US)",
volume = "182",
pages = "4917--4930",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "8",

}

TY - JOUR

T1 - A novel hybrid yeast-human network analysis reveals an essential role for FNBP1L in antibacterial autophagy

AU - Huett, Alan

AU - Ng, Aylwin

AU - Cao, Zhifang

AU - Kuballa, Petric

AU - Komatsu, Masaaki

AU - Daly, Mark J.

AU - Podolsky, Daniel K.

AU - Xavier, Ramnik J.

PY - 2009/4/15

Y1 - 2009/4/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=65249185812&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=65249185812&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.0803050

DO - 10.4049/jimmunol.0803050

M3 - Article

C2 - 19342671

AN - SCOPUS:65249185812

VL - 182

SP - 4917

EP - 4930

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 8

ER -