3 Genetics of the Unfolded Protein Response in Fungi
REBEKKA HARTING
1
, KAI HEIMEL
1
CONTENTS
I. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
II. General Concept of the UPR . . . . . . . . . . . . . . . . . 49
A. Common Principles of UPR Signaling . . . . . 49
B. Ire1 and Hac1: Key Players of the UPR . . . . 50
III. The UPR in Fungal Pathogens . . . . . . . . . . . . . . . 55
A. The UPR in Human Pathogenic Fungi . . . . 55
B. The UPR in Plant Pathogenic Fungi . . . . . . . 59
IV. Connections and Interplay Between the UPR
and Other Signaling Pathways . . . . . . . . . . . . . . . 62
A. UPR and ERAD . . . . . . . . . . . . . . . . . . . . . . . . . . . 62
B. UPR and Autophagy . . . . . . . . . . . . . . . . . . . . . . 64
C. UPR and the Cell Wall Integrity Pathway . . 64
D. UPR and MAPK Signaling . . . . . . . . . . . . . . . . 65
E. UPR and Hypoxia . . . . . . . . . . . . . . . . . . . . . . . . . 65
V. The UPR in Biotechnology of Filamentous
Fungi . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66
A. Aspergillus niger . . . . . . . . . . . . . . . . . . . . . . . . . . 66
B. Trichoderma reesei . . . . . . . . . . . . . . . . . . . . . . . . 67
C. Neurospora crassa . . . . . . . . . . . . . . . . . . . . . . . . . 67
VI. Conclusion and Outlook . . . . . . . . . . . . . . . . . . . . . 68
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68
I. Introduction
Fungi inhabit almost all ecological niches on
earth and exhibit a wide variety of different
lifestyles, requiring efficient strategies to adapt
the intracellular signaling pathways to the
extracellular environment. Secretion of proteinaceous molecules including cell wall components and enzymes for nutrient mobilization
and/or for interaction with other organisms is
dependent on their correct folding, processing,
and transfer within the secretory pathway. The
unfolded protein response (UPR) is a conserved pathway in eukaryotic organisms. It
functions as a central regulatory instance
required for homeostasis of the endoplasmic
reticulum (ER) by adapting the ER folding
capacity to increased folding demands,
reflected by the accumulation of un- or misfolded protein aggregates in the ER. After its
initial discovery in the 1990s, it has become
evident that the UPR features a unique mechanism for signal transduction, referred to as
unconventional cytoplasmic splicing, to rapidly
adapt the transcriptional program and initiate a
comprehensive restructuring of the secretory
pathway. The UPR is of central importance for
saprotrophic growth of filamentous fungi and
for disease development in human and plant
pathogenic fungi, as well as in the optimization
of protein production within industrial settings
of fungal biotechnology. Comprehensive cellular and transcriptomic studies uncovered intricate connections between the UPR and other
conserved signaling pathways including autophagy, the cell wall integrity (CWI) pathway,
hypoxia adaptation, and even the control of
fungal development. Focusing on the UPR in
various model organisms, the basic principles,
physiological roles, but also specific functions,
interactions, and applications of the UPR will
be discussed.
II. General Concept of the UPR
A. Common Principles of UPR Signaling
The unfolded protein response represents a
safeguarding mechanism that protects the cell
1 Institut fu ¨r Mikrobiologie und Genetik, Abteilung Molekulare Mikrobiologie und Genetik, Go ¨ttinger Zentrum fu ¨r Molekulare Biowissenschaften (GZMB), Georg-August-Universita ¨t
Go ¨ttingen, Go ¨ttingen, Germany; e-mail: kheimel@gwdg.de
Genetics and Biotechnology, 3 rd Edition
The Mycota II
J.P. Benz, K. Schipper (Eds.)
© Springer Nature Switzerland AG 2020
REBEKKA HARTING
1
, KAI HEIMEL
1
CONTENTS
I. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
II. General Concept of the UPR . . . . . . . . . . . . . . . . . 49
A. Common Principles of UPR Signaling . . . . . 49
B. Ire1 and Hac1: Key Players of the UPR . . . . 50
III. The UPR in Fungal Pathogens . . . . . . . . . . . . . . . 55
A. The UPR in Human Pathogenic Fungi . . . . 55
B. The UPR in Plant Pathogenic Fungi . . . . . . . 59
IV. Connections and Interplay Between the UPR
and Other Signaling Pathways . . . . . . . . . . . . . . . 62
A. UPR and ERAD . . . . . . . . . . . . . . . . . . . . . . . . . . . 62
B. UPR and Autophagy . . . . . . . . . . . . . . . . . . . . . . 64
C. UPR and the Cell Wall Integrity Pathway . . 64
D. UPR and MAPK Signaling . . . . . . . . . . . . . . . . 65
E. UPR and Hypoxia . . . . . . . . . . . . . . . . . . . . . . . . . 65
V. The UPR in Biotechnology of Filamentous
Fungi . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66
A. Aspergillus niger . . . . . . . . . . . . . . . . . . . . . . . . . . 66
B. Trichoderma reesei . . . . . . . . . . . . . . . . . . . . . . . . 67
C. Neurospora crassa . . . . . . . . . . . . . . . . . . . . . . . . . 67
VI. Conclusion and Outlook . . . . . . . . . . . . . . . . . . . . . 68
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68
I. Introduction
Fungi inhabit almost all ecological niches on
earth and exhibit a wide variety of different
lifestyles, requiring efficient strategies to adapt
the intracellular signaling pathways to the
extracellular environment. Secretion of proteinaceous molecules including cell wall components and enzymes for nutrient mobilization
and/or for interaction with other organisms is
dependent on their correct folding, processing,
and transfer within the secretory pathway. The
unfolded protein response (UPR) is a conserved pathway in eukaryotic organisms. It
functions as a central regulatory instance
required for homeostasis of the endoplasmic
reticulum (ER) by adapting the ER folding
capacity to increased folding demands,
reflected by the accumulation of un- or misfolded protein aggregates in the ER. After its
initial discovery in the 1990s, it has become
evident that the UPR features a unique mechanism for signal transduction, referred to as
unconventional cytoplasmic splicing, to rapidly
adapt the transcriptional program and initiate a
comprehensive restructuring of the secretory
pathway. The UPR is of central importance for
saprotrophic growth of filamentous fungi and
for disease development in human and plant
pathogenic fungi, as well as in the optimization
of protein production within industrial settings
of fungal biotechnology. Comprehensive cellular and transcriptomic studies uncovered intricate connections between the UPR and other
conserved signaling pathways including autophagy, the cell wall integrity (CWI) pathway,
hypoxia adaptation, and even the control of
fungal development. Focusing on the UPR in
various model organisms, the basic principles,
physiological roles, but also specific functions,
interactions, and applications of the UPR will
be discussed.
II. General Concept of the UPR
A. Common Principles of UPR Signaling
The unfolded protein response represents a
safeguarding mechanism that protects the cell
1 Institut fu ¨r Mikrobiologie und Genetik, Abteilung Molekulare Mikrobiologie und Genetik, Go ¨ttinger Zentrum fu ¨r Molekulare Biowissenschaften (GZMB), Georg-August-Universita ¨t
Go ¨ttingen, Go ¨ttingen, Germany; e-mail: kheimel@gwdg.de
Genetics and Biotechnology, 3 rd Edition
The Mycota II
J.P. Benz, K. Schipper (Eds.)
© Springer Nature Switzerland AG 2020