E3 ligase Hei10: a multifaceted structure-based signaling molecule with roles within and beyond meiosis.
Human enhancer of invasion-10 (Hei10) mediates meiotic recombination and also plays roles in cell proliferation. Here we explore Hei10's roles throughout the sexual cycle of the fungus Sordaria with respect to localization and effects of null, RING-binding, and putative cyclin-binding (RXL) domain mutations. Hei10 makes three successive types of foci. Early foci form along synaptonemal complex (SC) central regions. At some of these positions, depending on its RING and RXL domains, Hei10 mediates development and turnover of two sequential types of recombination complexes, each demarked by characteristic amplified Hei10 foci. Integration with ultrastructural data for recombination nodules further reveals that recombination complexes differentiate into three types, one of which corresponds to crossover recombination events during or prior to SC formation. Finally, Hei10 positively and negatively modulates SUMO localization along SCs by its RING and RXL domains, respectively. The presented findings suggest that Hei10 integrates signals from the SC, associated recombination complexes, and the cell cycle to mediate both the development and programmed turnover/evolution of recombination complexes via SUMOylation/ubiquitination. Analogous cell cycle-linked assembly/disassembly switching could underlie localization and roles for Hei10 in centrosome/spindle pole body dynamics and associated nuclear trafficking. We suggest that Hei10 is a unique type of structure-based signal transduction protein.
UMR 8621, Institut de Génétique et Microbiologie, Université Paris-Sud, 91405 Orsay, France; Institut Curie, 75248 Paris Cedex 05, France;
Arnaud
A
De Muyt
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA;
Liangran
L
Zhang
UMR 3215, INSERM U934, Institut Curie, 75005 Paris, France.
Tristan
T
Piolot
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA;
Nancy
N
Kleckner
UMR 8621, Institut de Génétique et Microbiologie, Université Paris-Sud, 91405 Orsay, France;
Eric
E
Espagne
UMR 8621, Institut de Génétique et Microbiologie, Université Paris-Sud, 91405 Orsay, France;
Denise
D
Zickler
D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D008540:Meiosis / Q000502:physiology*; D009154:Mutation; D017434:Protein Structure, Tertiary / Q000235:genetics; D011995:Recombination, Genetic / Q000235:genetics; D025842:SUMO-1 Protein / Q000378:metabolism; D015398:Signal Transduction; D020037:Sordariales / Q000201:enzymology* / Q000235:genetics*; D013573:Synaptonemal Complex / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*
D005656:Fungal Proteins; D025842:SUMO-1 Protein; D044767:Ubiquitin-Protein Ligases
Hei10; meiosis; recombination; spindle pole body/centrosome; synaptonemal complex