Entity

Time filter

Source Type


Glick B.S.,University of Chicago | Luini A.,Telethon Institute of Genetics and Medicine
Cold Spring Harbor Perspectives in Biology | Year: 2011

Avariety of secretory cargoes move through the Golgi, but the pathways and mechanisms of this traffic are still being debated. Here, we evaluate the strengths and weaknesses of five current models for Golgi traffic: (1) anterograde vesicular transport between stable compartments, (2) cisternal progression/maturation, (3) cisternal progression/maturation with heterotypic tubular transport, (4) rapid partitioning in a mixed Golgi, and (5) stable compartments as cisternal progenitors. Each model is assessed for its ability to explain a set of key observations encompassing multiple cell types. No single model can easily explain all of the observations from diverse organisms. However, we propose that cisternal progression/ maturation is the best candidate for a conserved core mechanism of Golgi traffic, and that some cells elaborate this core mechanism by means of heterotypic tubular transport between cisternae. © 2011 Cold Spring Harbor Laboratory Press. Source


Sutterlin C.,University of California at Irvine | Colanzi A.,Consorzio Mario Negri Sud | Colanzi A.,Telethon Institute of Genetics and Medicine | Colanzi A.,National Research Council Italy
Journal of Cell Biology | Year: 2010

The mammalian Golgi apparatus is characterized by a ribbon-like organization adjacent to the centrosome during interphase and extensive fragmentation and dispersal away from the centrosome during mitosis. It is not clear whether this dynamic association between the Golgi and centrosome is of functional significance. We discuss recent findings indicating that the Golgi-centrosome relationship may be important for directional protein transport and centrosome positioning, which are both required for cell polarization. We also summarize our current knowledge of the link between Golgi organization and cell cycle progression. © 2010 Sütterlin and Colanzi. Source


Nakano A.,University of Tokyo | Nakano A.,RIKEN | Luini A.,Telethon Institute of Genetics and Medicine
Current Opinion in Cell Biology | Year: 2010

There are, in theory, several ways in which proteins may pass through the Golgi apparatus. Among these, the cisternal progression-maturation mode has gained broad consensus. However, there remain questions regarding the molecular mechanisms by which resident proteins are sorted from cargo and move backward to the proximal cisterna in synchrony with cisternal progression. In this short review, we discuss current questions about the organisation of trafficking to, through, and out of the Golgi apparatus, as well as the main approaches being developed to address such questions in model organisms including yeast, mammals and plants. © 2010 Elsevier Ltd. Source


de Leo M.G.,Telethon Institute of Genetics and Medicine
Nature Cell Biology | Year: 2016

Phosphoinositides (PtdIns) control fundamental cell processes, and inherited defects of PtdIns kinases or phosphatases cause severe human diseases, including Lowe syndrome due to mutations in OCRL, which encodes a PtdIns(4,5)P2 5-phosphatase. Here we unveil a lysosomal response to the arrival of autophagosomal cargo in which OCRL plays a key part. We identify mitochondrial DNA and TLR9 as the cargo and the receptor that triggers and mediates, respectively, this response. This lysosome-cargo response is required to sustain the autophagic flux and involves a local increase in PtdIns(4,5)P2 that is confined in space and time by OCRL. Depleting or inhibiting OCRL leads to an accumulation of lysosomal PtdIns(4,5)P2, an inhibitor of the calcium channel mucolipin-1 that controls autophagosome–lysosome fusion. Hence, autophagosomes accumulate in OCRL-depleted cells and in the kidneys of Lowe syndrome patients. Importantly, boosting the activity of mucolipin-1 with selective agonists restores the autophagic flux in cells from Lowe syndrome patients. © 2016 Nature Publishing Group Source


Polishchuk R.,Telethon Institute of Genetics and Medicine | Lutsenko S.,Johns Hopkins University
Histochemistry and Cell Biology | Year: 2013

Copper is essential for a variety of important biological processes as a cofactor and regulator of many enzymes. Incorporation of copper into the secreted and plasma membrane-targeted cuproenzymes takes place in Golgi, a compartment central for normal copper homeostasis. The Golgi complex harbors copper-transporting ATPases, ATP7A and ATP7B that transfer copper from the cytosol into Golgi lumen for incorporation into copper-dependent enzymes. The Golgi complex also sends these ATPases to appropriate post-Golgi destinations to ensure correct Cu fluxes in the body and to avoid potentially toxic copper accumulation. Mutations in ATP7A or ATP7B or in the proteins that regulate their trafficking affect their exit from Golgi or subsequent retrieval to this organelle. This, in turn, disrupts the homeostatic Cu balance, resulting in copper deficiency (Menkes disease) or copper overload (Wilson disease). Research over the last decade has yielded significant insights into the enzymatic properties and cell biology of the copper ATPases. However, the mechanisms through which the Golgi regulates trafficking of ATP7A/7B and, therefore, maintains Cu homeostasis remain unclear. This review summarizes current data on the role of the Golgi in Cu metabolism and outlines questions and challenges that should be addressed to understand ATP7A and ATP7B trafficking mechanisms in health and disease. © 2013 Springer-Verlag Berlin Heidelberg. Source

Discover hidden collaborations