The novel microtubule-associated cap-glycine protein cgp1 governs growth, differentiation, and virulence of cryptococcus neoformans

Li Li Wanga, Kyung Tae Lee, Kwang Woo Jung, Dong Gi Lee, Yong-Sun Bahn

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Microtubules are involved in mechanical support, cytoplasmic organization, and several cellular processes by interacting with diverse microtubule-associated proteins such as plus-end tracking proteins, motor proteins, and tubulin-folding cofactors. A number of the cytoskeletonassociated proteins (CAPs) contain the CAP-glycine-rich (CAP-Gly) domain, which is evolutionarily conserved and generally considered to bind to a-tubulin to regulate the function of microtubules. However, there has been a dearth of research on CAP-Gly proteins in fungal pathogens, including Cryptococcus neoformans, which is a global cause of fatal meningoencephalitis in immunocompromised patients. In this study, we identified five CAPGly protein-encoding genes in C. neoformans. Among these, Cgp1 encoded by CNAG_06352 has a unique domain structure containing CAP-Gly, SPEC, and Spc7 domains that is not orthologous to CAPs in other eukaryotes. Supporting the role of Cgp1 in microtubule-related function, we demonstrate that deletion or overexpression of CGP1 alters cellular susceptibility to thiabendazole, a microtubule destabilizer and that Cgp1 is co-localized with cytoplasmic microtubules. Related to the cellular function of microtubules, Cgp1 governs the maintenance of membrane stability and genotoxic stress responses. Deletion of CGP1 also reduces production of melanin pigment and attenuates the virulence of C. neoformans. Furthermore, we demonstrate that Cgp1 uniquely regulates the sexual differentiation of C. neoformans with distinct roles in the early and late stage of mating. Domain analysis revealed that the CAP-Gly domain plays a major role in all Cgp1 functions examined. In conclusion, this novel CAP-Gly protein, Cgp1, has pleotropic roles in regulating growth, stress responses, differentiation, and virulence in C. neoformans.

Original languageEnglish
Pages (from-to)566-584
Number of pages19
JournalVirulence
Volume9
Issue number1
DOIs
Publication statusPublished - 2018 Jan 1

Fingerprint

Cryptococcus neoformans
Microtubules
Glycine
Virulence
Growth
Proteins
Tubulin
Thiabendazole
Sex Differentiation
Meningoencephalitis
Microtubule-Associated Proteins
Fungal Proteins
Protein Folding
Melanins
Immunocompromised Host
Eukaryota
DNA Damage
Maintenance
Membranes

All Science Journal Classification (ASJC) codes

  • Parasitology
  • Microbiology
  • Immunology
  • Microbiology (medical)
  • Infectious Diseases

Cite this

Wanga, Li Li ; Lee, Kyung Tae ; Jung, Kwang Woo ; Lee, Dong Gi ; Bahn, Yong-Sun. / The novel microtubule-associated cap-glycine protein cgp1 governs growth, differentiation, and virulence of cryptococcus neoformans. In: Virulence. 2018 ; Vol. 9, No. 1. pp. 566-584.
@article{8120228e763f4e9597790a2ce10cce0d,
title = "The novel microtubule-associated cap-glycine protein cgp1 governs growth, differentiation, and virulence of cryptococcus neoformans",
abstract = "Microtubules are involved in mechanical support, cytoplasmic organization, and several cellular processes by interacting with diverse microtubule-associated proteins such as plus-end tracking proteins, motor proteins, and tubulin-folding cofactors. A number of the cytoskeletonassociated proteins (CAPs) contain the CAP-glycine-rich (CAP-Gly) domain, which is evolutionarily conserved and generally considered to bind to a-tubulin to regulate the function of microtubules. However, there has been a dearth of research on CAP-Gly proteins in fungal pathogens, including Cryptococcus neoformans, which is a global cause of fatal meningoencephalitis in immunocompromised patients. In this study, we identified five CAPGly protein-encoding genes in C. neoformans. Among these, Cgp1 encoded by CNAG_06352 has a unique domain structure containing CAP-Gly, SPEC, and Spc7 domains that is not orthologous to CAPs in other eukaryotes. Supporting the role of Cgp1 in microtubule-related function, we demonstrate that deletion or overexpression of CGP1 alters cellular susceptibility to thiabendazole, a microtubule destabilizer and that Cgp1 is co-localized with cytoplasmic microtubules. Related to the cellular function of microtubules, Cgp1 governs the maintenance of membrane stability and genotoxic stress responses. Deletion of CGP1 also reduces production of melanin pigment and attenuates the virulence of C. neoformans. Furthermore, we demonstrate that Cgp1 uniquely regulates the sexual differentiation of C. neoformans with distinct roles in the early and late stage of mating. Domain analysis revealed that the CAP-Gly domain plays a major role in all Cgp1 functions examined. In conclusion, this novel CAP-Gly protein, Cgp1, has pleotropic roles in regulating growth, stress responses, differentiation, and virulence in C. neoformans.",
author = "Wanga, {Li Li} and Lee, {Kyung Tae} and Jung, {Kwang Woo} and Lee, {Dong Gi} and Yong-Sun Bahn",
year = "2018",
month = "1",
day = "1",
doi = "10.1080/21505594.2017.1423189",
language = "English",
volume = "9",
pages = "566--584",
journal = "Virulence",
issn = "2150-5594",
publisher = "Landes Bioscience",
number = "1",

}

The novel microtubule-associated cap-glycine protein cgp1 governs growth, differentiation, and virulence of cryptococcus neoformans. / Wanga, Li Li; Lee, Kyung Tae; Jung, Kwang Woo; Lee, Dong Gi; Bahn, Yong-Sun.

In: Virulence, Vol. 9, No. 1, 01.01.2018, p. 566-584.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The novel microtubule-associated cap-glycine protein cgp1 governs growth, differentiation, and virulence of cryptococcus neoformans

AU - Wanga, Li Li

AU - Lee, Kyung Tae

AU - Jung, Kwang Woo

AU - Lee, Dong Gi

AU - Bahn, Yong-Sun

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Microtubules are involved in mechanical support, cytoplasmic organization, and several cellular processes by interacting with diverse microtubule-associated proteins such as plus-end tracking proteins, motor proteins, and tubulin-folding cofactors. A number of the cytoskeletonassociated proteins (CAPs) contain the CAP-glycine-rich (CAP-Gly) domain, which is evolutionarily conserved and generally considered to bind to a-tubulin to regulate the function of microtubules. However, there has been a dearth of research on CAP-Gly proteins in fungal pathogens, including Cryptococcus neoformans, which is a global cause of fatal meningoencephalitis in immunocompromised patients. In this study, we identified five CAPGly protein-encoding genes in C. neoformans. Among these, Cgp1 encoded by CNAG_06352 has a unique domain structure containing CAP-Gly, SPEC, and Spc7 domains that is not orthologous to CAPs in other eukaryotes. Supporting the role of Cgp1 in microtubule-related function, we demonstrate that deletion or overexpression of CGP1 alters cellular susceptibility to thiabendazole, a microtubule destabilizer and that Cgp1 is co-localized with cytoplasmic microtubules. Related to the cellular function of microtubules, Cgp1 governs the maintenance of membrane stability and genotoxic stress responses. Deletion of CGP1 also reduces production of melanin pigment and attenuates the virulence of C. neoformans. Furthermore, we demonstrate that Cgp1 uniquely regulates the sexual differentiation of C. neoformans with distinct roles in the early and late stage of mating. Domain analysis revealed that the CAP-Gly domain plays a major role in all Cgp1 functions examined. In conclusion, this novel CAP-Gly protein, Cgp1, has pleotropic roles in regulating growth, stress responses, differentiation, and virulence in C. neoformans.

AB - Microtubules are involved in mechanical support, cytoplasmic organization, and several cellular processes by interacting with diverse microtubule-associated proteins such as plus-end tracking proteins, motor proteins, and tubulin-folding cofactors. A number of the cytoskeletonassociated proteins (CAPs) contain the CAP-glycine-rich (CAP-Gly) domain, which is evolutionarily conserved and generally considered to bind to a-tubulin to regulate the function of microtubules. However, there has been a dearth of research on CAP-Gly proteins in fungal pathogens, including Cryptococcus neoformans, which is a global cause of fatal meningoencephalitis in immunocompromised patients. In this study, we identified five CAPGly protein-encoding genes in C. neoformans. Among these, Cgp1 encoded by CNAG_06352 has a unique domain structure containing CAP-Gly, SPEC, and Spc7 domains that is not orthologous to CAPs in other eukaryotes. Supporting the role of Cgp1 in microtubule-related function, we demonstrate that deletion or overexpression of CGP1 alters cellular susceptibility to thiabendazole, a microtubule destabilizer and that Cgp1 is co-localized with cytoplasmic microtubules. Related to the cellular function of microtubules, Cgp1 governs the maintenance of membrane stability and genotoxic stress responses. Deletion of CGP1 also reduces production of melanin pigment and attenuates the virulence of C. neoformans. Furthermore, we demonstrate that Cgp1 uniquely regulates the sexual differentiation of C. neoformans with distinct roles in the early and late stage of mating. Domain analysis revealed that the CAP-Gly domain plays a major role in all Cgp1 functions examined. In conclusion, this novel CAP-Gly protein, Cgp1, has pleotropic roles in regulating growth, stress responses, differentiation, and virulence in C. neoformans.

UR - http://www.scopus.com/inward/record.url?scp=85049114997&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85049114997&partnerID=8YFLogxK

U2 - 10.1080/21505594.2017.1423189

DO - 10.1080/21505594.2017.1423189

M3 - Article

VL - 9

SP - 566

EP - 584

JO - Virulence

JF - Virulence

SN - 2150-5594

IS - 1

ER -