Flotillin FloA protects fungal cells from calcium stress by driving PmaA internalization

When the model fungus Aspergillus nidulans is exposed to calcium stress, a lipid raft marker protein called FloA triggers the internalization of a key membrane enzyme, and this relocalization is what keeps the cells alive, according to a new study in PLOS Genetics by Moemi Kawashima, Thomas Krüger and colleagues.

Lipid rafts are specialized microdomains within biological membranes that act as organizational platforms, clustering signaling molecules and modulating membrane protein conformation through their distinct lipid environment. Several marker proteins define these rafts, but the functions of some remain obscure. One such protein is flotillin, which has been linked to endocytosis. The researchers investigated FloA, the sole flotillin homolog in A. nidulans, and found that its expression is specifically upregulated in response to calcium stress, a regulatory pattern also conserved in the related pathogenic fungus Aspergillus fumigatus.

To identify FloA’s interaction partners, the team used BioID proximity labeling. This revealed that FloA physically interacts with proteins in the endocytic pathway as well as with another lipid raft marker: the plasma membrane H+-ATPase PmaA. Under calcium stress, PmaA undergoes internalization from the cytoplasmic membrane. However, when the floA gene is deleted, this internalization is prevented and the cells die. The same lethal phenotype could be mimicked by treating cells with an endocytosis inhibitor during calcium stress, indicating that active endocytosis is required for the protective response.

Together, the findings demonstrate that FloA is essential for the internalization of PmaA during calcium stress, a process that prevents intracellular calcium overload and promotes cell viability. The study also adds further evidence for flotillin-assisted endocytosis, clarifying a function for a long-enigmatic lipid raft marker protein and showing that relocalization of a membrane ATPase, orchestrated by FloA, is a protective response to calcium stress in fungi.

Subject of Research: The role of the lipid raft marker FloA in protecting fungi from calcium stress through PmaA internalization

Article Title: The lipid raft marker flotillin FloA drives relocalization of the plasma membrane H + -ATPase PmaA as a protective response to calcium stress

Article References: Kawashima, M., Krüger, T., Rosin, M., Tröger-Görler, S., Heinekamp, T., & Brakhage, A. A. (2026). The lipid raft marker flotillin FloA drives relocalization of the plasma membrane H+-ATPase PmaA as a protective response to calcium stress. PLOS Genetics, 22(10), e1012147. https://doi.org/10.1371/journal.pgen.1012147

Image Credits: AI Generated

DOI: 10.1371/journal.pgen.1012147

Keywords: Aspergillus nidulans, Aspergillus fumigatus, flotillin, FloA, lipid rafts, PmaA, H+-ATPase, endocytosis, calcium stress, BioID proximity labeling, PmaA internalization, cell viability