title: Protein SUMOylation is Involved in Cell-cycle Progression and Cell Morphology in Giardia lamblia.
abstract: The unicellular protozoa Giardia lamblia is a food- and waterborne parasite that causes giardiasis. This illness is manifested as acute and self-limited diarrhea and can evolve to long-term complications. Successful establishment of infection by Giardia trophozoites requires adhesion to host cells and colonization of the small intestine, where parasites multiply by mitotic division. The tight binding of trophozoites to host cells occurs by means of the ventral adhesive disc, a spiral array of microtubules and associated proteins such as giardins. In this work we show that knock down of the Small Ubiquitin-like MOdifier (SUMO) results in less adhesive trophzoites, decreased cell proliferation and deep morphological alterations, including at the ventral disc. Consistent with the reduced proliferation, SUMO knocked-down trophozoites were arrested in G1 and in S phases of the cell cycle. Mass spectrometry analysis of anti-SUMO immunoprecipitates was performed to identify SUMO substrates possibly involved in these events. Among the identified SUMOylation targets, α-tubulin was further validated by Western blot and confirmed to be a SUMO target in Giardia trophozoites.
authors.affiliation: Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, RuaBotucatu 862, 04023-062, Vila Clementino, São Paulo, SP, Brazil.
authors.forename: Bruno M
authors.initials: BM
authors.lastname: Di Genova
authors.affiliation: Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, RuaBotucatu 862, 04023-062, Vila Clementino, São Paulo, SP, Brazil.
authors.forename: Richard C
authors.initials: RC
authors.lastname: da Silva
authors.affiliation: Laboratório Especial de Ciclo Celular, Centro de Toxinas, Resposta Imune e Sinalização Celular - CeTICS, Instituto Butantan, Avenida Vital Brasil 1500, 05503-900, Butantã, São Paulo, SP, Brazil.
authors.forename: Júlia P C
authors.initials: JPC
authors.lastname: da Cunha
authors.affiliation: Laboratorio de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad Católica de Córdoba (UCC), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Av. Armada Argentina 3555., X5016DHK, Cordoba, Argentina.
authors.forename: Pablo R
authors.initials: PR
authors.lastname: Gargantini
authors.affiliation: Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, RuaBotucatu 862, 04023-062, Vila Clementino, São Paulo, SP, Brazil.
authors.forename: Renato A
authors.initials: RA
authors.lastname: Mortara
authors.affiliation: Departamento de Ciências Biológicas, Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo, Rua São Nicolau 210, 09913-030, Diadema, SP, Brazil.
authors.forename: Renata R
authors.initials: RR
authors.lastname: Tonelli
mesh_terms: D002453:Cell Cycle; D055785:Gene Knockdown Techniques; D016829:Giardia lamblia / Q000378:metabolism / Q000502:physiology*; D013058:Mass Spectrometry; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism; D025841:Small Ubiquitin-Related Modifier Proteins / Q000235:genetics* / Q000378:metabolism; D058207:Sumoylation; D053058:Trophozoites / Q000502:physiology; D014404:Tubulin / Q000378:metabolism*
chemical_list: D015800:Protozoan Proteins; D025841:Small Ubiquitin-Related Modifier Proteins; D014404:Tubulin
keywords: Cell division; cytoskeleton; mass spectrometry; post-translational modification; protozoan; small-ubiquitin-like modifier; tubulin