scholarly journals Cex1 is a new component of the COPI Golgi-to-vacuole intracellular trafficking machinery

2018 ◽  
Author(s):  
Ludovic Enkler ◽  
Johann Owen de Craene ◽  
Bruno Rinaldi ◽  
Philippe Hammann ◽  
Osamu Nureki ◽  
...  
Keyword(s):  
Neurodegenerative Disorders ◽  
Intracellular Trafficking ◽  
Complex I ◽  
Fluorescent Microscopy ◽  
Nuclear Periphery ◽  
Interacting Proteins ◽  
Trafficking Pathway ◽  
Sorting Receptor ◽  
Vacuolar Protein ◽  
Golgi Network

AbstractDuring translational elongation, aminoacylated tRNA are supplied to the ribosome by RNA-interacting proteins. Cex1, a HEAT-containing protein, has been shown to participate to this tRNA channeling by interacting with aminoacylated tRNA during their export from the nucleus. Here, we show that Cex1 is a component of COPI (coatomer complex I) coated vesicles involved in the Golgi-to-vacuole trafficking pathway in Saccharomyces cerevisiae. Cex1 interacts with key components of the COPI coat Sec27, Sec28 and Sec33 proteins. Moreover, fluorescent microscopy indicates that Cex1 is not localized at the nuclear periphery as expected for an effector of nuclear tRNA channeling, but is observed on endosomal trans-Golgi network (TGN) positive structures. This localization relies on the vacuolar protein sorting receptor Vps10. Our data not only resolve the functional ambiguity regarding Cex1 homologues across species, but also point to the possibility to develop yeast-based models to study neurodegenerative disorders linked to the Human Cex1 homologue SCYL1.

scholarly journals Cex1 is a component of the COPI intracellular trafficking machinery

Biology Open ◽  
2021 ◽  
Vol 10 (3) ◽  
Author(s):  
Ludovic Enkler ◽  
Bruno Rinaldi ◽  
Johan Owen de Craene ◽  
Philippe Hammann ◽  
Osamu Nureki ◽  
...  
Keyword(s):  
Neurodegenerative Disorders ◽  
Intracellular Trafficking ◽  
Complex I ◽  
Mammalian Cells ◽  
Deletion Mutant ◽  
Protein Glycosylation ◽  
Coated Vesicles ◽  
Human Homologue ◽  
Membrane Compartments ◽  
Mutant Cells

ABSTRACT COPI (coatomer complex I) coated vesicles are involved in Golgi-to-ER and intra-Golgi trafficking pathways, and mediate retrieval of ER resident proteins. Functions and components of the COPI-mediated trafficking pathways, beyond the canonical set of Sec/Arf proteins, are constantly increasing in number and complexity. In mammalian cells, GORAB, SCYL1 and SCYL3 proteins regulate Golgi morphology and protein glycosylation in concert with the COPI machinery. Here, we show that Cex1, homologous to the mammalian SCYL proteins, is a component of the yeast COPI machinery, by interacting with Sec27, Sec28 and Sec33 (Ret1/Cop1) proteins of the COPI coat. Cex1 was initially reported to mediate channeling of aminoacylated tRNA outside of the nucleus. Our data show that Cex1 localizes at membrane compartments, on structures positive for the Sec33 α-COP subunit. Moreover, the Wbp1 protein required for N-glycosylation and interacting via its di-lysine motif with the Sec27 β′-COP subunit is mis-targeted in cex1Δ deletion mutant cells. Our data point to the possibility of developing Cex1 yeast-based models to study neurodegenerative disorders linked to pathogenic mutations of its human homologue SCYL1.

scholarly journals The Plant Vacuolar Sorting Receptor Atelp Is Involved in Transport of Nh2-Terminal Propeptide-Containing Vacuolar Proteins in Arabidopsis thaliana

2000 ◽  
Vol 149 (7) ◽  
pp. 1335-1344 ◽  
Author(s):  
Sharif U. Ahmed ◽  
Enrique Rojo ◽  
Valentina Kovaleva ◽  
Sridhar Venkataraman ◽  
James E. Dombrowski ◽  
...  
Keyword(s):  
Arabidopsis Thaliana ◽  
Transgenic Arabidopsis ◽  
Sorting Signals ◽  
Specific Manner ◽  
Vacuolar Sorting Receptor ◽  
Vacuolar Sorting ◽  
Sorting Receptor ◽  
Vacuolar Protein ◽  
Golgi Network ◽  
Endogenous Plant

Many soluble plant vacuolar proteins are sorted away from secreted proteins into small vesicles at the trans-Golgi network by transmembrane cargo receptors. Cleavable vacuolar sorting signals include the NH2-terminal propeptide (NTPP) present in sweet potato sporamin (Spo) and the COOH-terminal propeptide (CTPP) present in barley lectin (BL). These two proteins have been found to be transported by different mechanisms to the vacuole. We examined the ability of the vacuolar cargo receptor AtELP to interact with the sorting signals of heterologous and endogenous plant vacuolar proteins in mediating vacuolar transport in Arabidopsis thaliana. AtELP extracted from microsomes was found to interact with the NTPPs of barley aleurain and Spo, but not with the CTPPs of BL or tobacco chitinase, in a pH-dependent and sequence-specific manner. In addition, EM studies revealed the colocalization of AtELP with NTPP-Spo at the Golgi apparatus, but not with BL-CTPP in roots of transgenic Arabidopsis plants. Further, we found that AtELP interacts in a similar manner with the NTPP of the endogenous vacuolar protein AtALEU (Arabidopsis thaliana Aleu), a protein highly homologous to barley aleurain. We hypothesize that AtELP functions as a vacuolar sorting receptor involved in the targeting of NTPP-, but not CTPP-containing proteins in Arabidopsis.

scholarly journals Small GTPases of the Rab and Arf Families: Key Regulators of Intracellular Trafficking in Neurodegeneration

2021 ◽  
Vol 22 (9) ◽  
pp. 4425
Author(s):  
Alazne Arrazola Arrazola Sastre ◽  
Miriam Luque Luque Montoro ◽  
Hadriano M. Lacerda ◽  
Francisco Llavero ◽  
José L. Zugaza
Keyword(s):  
Membrane Trafficking ◽  
Neurodegenerative Disorders ◽  
Synaptic Vesicles ◽  
Intracellular Trafficking ◽  
Small Gtpases ◽  
Constant Flow ◽  
Parkinson’S Diseases ◽  
The Central Nervous System ◽  
Arf Gtpases

Small guanosine triphosphatases (GTPases) of the Rab and Arf families are key regulators of vesicle formation and membrane trafficking. Membrane transport plays an important role in the central nervous system. In this regard, neurons require a constant flow of membranes for the correct distribution of receptors, for the precise composition of proteins and organelles in dendrites and axons, for the continuous exocytosis/endocytosis of synaptic vesicles and for the elimination of dysfunctional proteins. Thus, it is not surprising that Rab and Arf GTPases have been associated with neurodegenerative diseases such as Alzheimer’s and Parkinson’s. Both pathologies share characteristics such as the presence of protein aggregates and/or the fragmentation of the Golgi apparatus, hallmarks that have been related to both Rab and Arf GTPases functions. Despite their relationship with neurodegenerative disorders, very few studies have focused on the role of these GTPases in the pathogenesis of neurodegeneration. In this review, we summarize their importance in the onset and progression of Alzheimer’s and Parkinson’s diseases, as well as their emergence as potential therapeutical targets for neurodegeneration.

scholarly journals Intracellular Trafficking Pathway of Yeast Long-chain Base Kinase Lcb4, from Its Synthesis to Its Degradation

2007 ◽  
Vol 282 (39) ◽  
pp. 28485-28492 ◽  
Author(s):  
Soichiro Iwaki ◽  
Takamitsu Sano ◽  
Tomoko Takagi ◽  
Masako Osumi ◽  
Akio Kihara ◽  
...  
Keyword(s):  
Intracellular Trafficking ◽  
Chain Base ◽  
Trafficking Pathway ◽  
Long Chain Base ◽  
Long Chain

scholarly journals BAIAP3, a C2 domain–containing Munc13 protein, controls the fate of dense-core vesicles in neuroendocrine cells

2017 ◽  
Vol 216 (7) ◽  
pp. 2151-2166 ◽  
Author(s):  
Xingmin Zhang ◽  
Shan Jiang ◽  
Kelly A. Mitok ◽  
Lingjun Li ◽  
Alan D. Attie ◽  
...  
Keyword(s):  
Neuroendocrine Cells ◽  
Dense Core ◽  
Dense Core Vesicle ◽  
Protein Homeostasis ◽  
C2 Domain ◽  
Β Cells ◽  
Calcium Dependent ◽  
Trafficking Pathway ◽  
Protein Receptor ◽  
Golgi Network

Dense-core vesicle (DCV) exocytosis is a SNARE (soluble N-ethylmaleimide–sensitive fusion attachment protein receptor)-dependent anterograde trafficking pathway that requires multiple proteins for regulation. Several C2 domain–containing proteins are known to regulate Ca2+-dependent DCV exocytosis in neuroendocrine cells. In this study, we identified others by screening all (∼139) human C2 domain–containing proteins by RNA interference in neuroendocrine cells. 40 genes were identified, including several encoding proteins with known roles (CAPS [calcium-dependent activator protein for secretion 1], Munc13-2, RIM1, and SYT10) and many with unknown roles. One of the latter, BAIAP3, is a secretory cell–specific Munc13-4 paralog of unknown function. BAIAP3 knockdown caused accumulation of fusion-incompetent DCVs in BON neuroendocrine cells and lysosomal degradation (crinophagy) of insulin-containing DCVs in INS-1 β cells. BAIAP3 localized to endosomes was required for Golgi trans-Golgi network 46 (TGN46) recycling, exhibited Ca2+-stimulated interactions with TGN SNAREs, and underwent Ca2+-stimulated TGN recruitment. Thus, unlike other Munc13 proteins, BAIAP3 functions indirectly in DCV exocytosis by affecting DCV maturation through its role in DCV protein recycling. Ca2+ rises that stimulate DCV exocytosis may stimulate BAIAP3-dependent retrograde trafficking to maintain DCV protein homeostasis and DCV function.

scholarly journals Intracellular trafficking pathway of newly synthesized CD1b molecules

2002 ◽  
Vol 21 (6) ◽  
pp. 1504-1504
Author(s):  
V. Briken ◽  
R.M. Jackman ◽  
S. Dasgupta ◽  
S. Hoening ◽  
S.A. Porcelli
Keyword(s):  
Intracellular Trafficking ◽  
Trafficking Pathway

Interaction of MAP17 with NHERF3/4 induces translocation of the renal Na/Pi IIa transporter to the trans-Golgi

2007 ◽  
Vol 292 (1) ◽  
pp. F230-F242 ◽  
Author(s):  
Miguel A. Lanaspa ◽  
Héctor Giral ◽  
Sophia Y. Breusegem ◽  
Nabil Halaihel ◽  
Goretti Baile ◽  
...  
Keyword(s):  
Pdz Domain ◽  
Phosphate Transport ◽  
Interacting Proteins ◽  
Opossum Kidney ◽  
Ok Cells ◽  
Kinase C ◽  
Important Intermediate ◽  
Pdz Protein ◽  
Golgi Network ◽  
Two Hybrid

The function of the NaPiIIa renal sodium-phosphate transporter is regulated through a complex network of interacting proteins. Several PDZ domain-containing proteins interact with its COOH terminus while the small membrane protein MAP17 interacts with its NH2 end. To elucidate the function of MAP17, we identified its interacting proteins using both bacterial and mammalian two-hybrid systems. Several PDZ domain-containing proteins, including the four NHERF proteins, as well as NaPiIIa and NHE3, were found to bind to MAP17. The interactions of MAP17 with the NHERF proteins and with NaPiIIa were further analyzed in opossum kidney (OK) cells. Expression of MAP17 alone had no effect on the NaPiIIa apical membrane distribution, but coexpression of MAP17 and NHERF3 or NHERF4 induced internalization of NaPiIIa, MAP17, and the PDZ protein to the trans-Golgi network (TGN). This effect was not observed when MAP17 was cotransfected with NHERF1/2 proteins. Inhibition of protein kinase C (PKC) prevented expression of the three proteins in the TGN. Activation of PKC in OK cells transfected only with MAP17 induced complete degradation of MAP17 and NaPiIIa. When lysosomal degradation was prevented, both proteins accumulated in the TGN. When the dopamine D1-like receptor was activated with fenoldopam, both NaPiIIa and MAP17 also accumulated in the TGN. Finally, cotransfection of MAP17 and NHERF3 prevented the adaptive upregulation of phosphate transport activity in OK cells in response to low extracellular phosphate. Therefore, the interaction between MAP17, NHERF3/4, and NaPiIIa in the TGN could be an important intermediate or alternate path in the internalization of NaPiIIa.

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