Giansanti Maria Grazia, Bonaccorsi Silvia, Kurek Roman, Farkas Rebecca M, Dimitri Patrizio, Fuller Margaret T, Gatti Maurizio
Dipartimento di Genetica e Biologia Molecolare, Istituto Pasteur-Fondazione Cenci Bolognetti, Istituto di Biologia e Patologia Molecolari del CNR, Università di Roma La Sapienza, P.le A. Moro 5, 00185 Roma, Italy.
Curr Biol. 2006 Jan 24;16(2):195-201. doi: 10.1016/j.cub.2005.12.011.
Phosphatidylinositol transfer proteins (PITPs) are highly conserved polypeptides that bind phosphatidylinositol or phosphatidylcholine monomers, facilitating their transfer from one membrane compartment to another . Although PITPs have been implicated in a variety of cellular functions, including lipid-mediated signaling and membrane trafficking, the precise biological roles of most PITPs remain to be elucidated . Here we show for the first time that a class I PITP is involved in cytokinesis. We found that giotto (gio), a Drosophila gene that encodes a class I PITP, serves an essential function required for both mitotic and meiotic cytokinesis. Neuroblasts and spermatocytes from gio mutants both assemble regular actomyosin rings. However, these rings fail to constrict to completion, leading to cytokinesis failures. Moreover, gio mutations cause an abnormal accumulation of Golgi-derived vesicles at the equator of spermatocyte telophases, suggesting that Gio is implicated in membrane-vesicle fusion. Consistent with these results, we found that Gio is enriched at the cleavage furrow, the ER, and the spindle envelope. We propose that Gio mediates transfer of lipid monomers from the ER to the equatorial membrane, causing a specific local enrichment in phosphatidylinositol. This change in membrane composition would ultimately facilitate vesicle fusion, allowing membrane addition to the furrow and/or targeted delivery of proteins required for cytokinesis.
磷脂酰肌醇转移蛋白（PITPs）是高度保守的多肽，可结合磷脂酰肌醇或磷脂酰胆碱单体，促进它们从一个膜区室转移到另一个膜区室。尽管PITPs参与了多种细胞功能，包括脂质介导的信号传导和膜运输，但大多数PITPs的确切生物学作用仍有待阐明。在这里，我们首次表明I类PITP参与胞质分裂。我们发现，giotto（gio）是果蝇中一个编码I类PITP的基因，对有丝分裂和减数分裂胞质分裂都是必需的。gio突变体的神经母细胞和精母细胞都能组装规则的肌动球蛋白环。然而，这些环无法完全收缩，导致胞质分裂失败。此外，gio突变导致高尔基体衍生的囊泡在精母细胞末期的赤道处异常积累，这表明Gio与膜-囊泡融合有关。与这些结果一致，我们发现Gio在分裂沟、内质网和纺锤体包膜处富集。我们提出，Gio介导脂质单体从内质网转移到赤道膜，导致磷脂酰肌醇在特定区域局部富集。膜成分的这种变化最终将促进囊泡融合，使膜添加到分裂沟和/或靶向递送胞质分裂所需的蛋白质。
