Accumulation of specific sterol precursors targets a MAP kinase cascade mediating cell-cell recognition and fusion.

TitleAccumulation of specific sterol precursors targets a MAP kinase cascade mediating cell-cell recognition and fusion.
Publication TypeJournal Article
Year of Publication2016
AuthorsWeichert, M, Lichius, A, Priegnitz, B-E, Brandt, U, Gottschalk, J, Nawrath, T, Groenhagen, U, Read, ND, Schulz, S, Flei├čner, A
JournalProc Natl Acad Sci U S A
Volume113
Issue42
Pagination11877-11882
Date Published2016 Oct 18
ISSN0027-8424
Abstract

Sterols are vital components of eukaryotic cell membranes. Defects in sterol biosynthesis, which result in the accumulation of precursor molecules, are commonly associated with cellular disorders and disease. However, the effects of these sterol precursors on the metabolism, signaling, and behavior of cells are only poorly understood. In this study, we show that the accumulation of only ergosterol precursors with a conjugated double bond in their aliphatic side chain specifically disrupts cell-cell communication and fusion in the fungus Neurospora crassa Genetically identical germinating spores of this fungus undergo cell-cell fusion, thereby forming a highly interconnected supracellular network during colony initiation. Before fusion, the cells use an unusual signaling mechanism that involves the coordinated and alternating switching between signal sending and receiving states of the two fusion partners. Accumulation of only ergosterol precursors with a conjugated double bond in their aliphatic side chain disrupts this coordinated cell-cell communication and suppresses cell fusion. These specific sterol precursors target a single ERK-like mitogen-activated protein (MAP) kinase (MAK-1)-signaling cascade, whereas a second MAP kinase pathway (MAK-2), which is also involved in cell fusion, is unaffected. These observations indicate that a minor specific change in sterol structure can exert a strong detrimental effect on a key signaling pathway of the cell, resulting in the absence of cell fusion.

DOI10.1073/pnas.1610527113
Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID27708165
PubMed Central IDPMC5081648