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Hedgehog Signaling Pathway02:33

Hedgehog Signaling Pathway

The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
Hedgehog Signaling Pathway02:33

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MAPK Signaling Cascades

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Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
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<i>Cryptococcus neoformans</i> rewires the conserved Wee1-CDK checkpoint through two divergent kinases required for replication-stress tolerance and virulence.

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Temporal Quantification of MAPK Induced Expression in Single Yeast Cells
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Deciphering subcellular localization-dependent functions of Hog1 MAPK in Cryptococcus neoformans.

Yu-Byeong Jang1, Yong-Sun Bahn1

  • 1Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea 03722.

Genetics
|May 18, 2026
PubMed
Summary

Hog1 protein compartmentalization in Cryptococcus neoformans dictates its function in stress adaptation, antifungal resistance, and virulence. Spatial control of Hog1 is crucial for fungal survival and pathogenesis.

Keywords:
CAAXHog1Nuclear localization signalfungal pathogenstress response

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Area of Science:

  • Mycology
  • Molecular Biology
  • Pathogen Biology

Background:

  • The Hog1 mitogen-activated protein kinase is vital for stress adaptation, differentiation, and virulence in the fungal pathogen Cryptococcus neoformans.
  • Understanding how Hog1's localization influences its specific functions is essential for developing targeted antifungal strategies.

Purpose of the Study:

  • To investigate the role of Hog1 protein compartmentalization in regulating its diverse functions within Cryptococcus neoformans.
  • To determine how restricting Hog1 to the nucleus or plasma membrane affects stress response, virulence, and development.

Main Methods:

  • Generated genetically engineered C. neoformans strains with localization-restricted Hog1 variants (membrane-tethered and constitutively nuclear).
  • Compared phenotypic traits, gene expression profiles, and intracellular glycerol levels of engineered strains with a functional Hog1 control.
  • Assessed responses to osmotic stress, ER stress, antifungal drugs, and developmental processes.

Main Results:

  • Membrane-tethered Hog1 restored thermotolerance and antifungal resistance but caused excessive glycerol accumulation.
  • Nuclear Hog1 was essential for osmotic and ER stress responses, capsule/melanin biosynthesis, and tunicamycin tolerance.
  • Hog1 localization influenced antifungal drug susceptibility and suppressed mating, indicating distinct roles in virulence and development.

Conclusions:

  • Hog1 compartmentalization is a critical determinant of its functional specificity in C. neoformans.
  • Spatiotemporal regulation of Hog1 activity is key for effective stress adaptation, antifungal resistance, and virulence.
  • Targeting Hog1 localization could offer novel therapeutic approaches against fungal meningitis.