Type IV P-type ATPases (P4-ATPases) are phospholipid flippases that translocate phospholipids from the exoplasmic (or luminal) to the cytoplasmic leaflet of lipid bilayers. In Saccharomyces cerevisiae, P4-ATPases are localized to specific subcellular compartments and play roles in compartment-mediated membrane trafficking; however, roles of mammalian P4-ATPases in membrane trafficking are poorly understood. We previously reported that ATP9A, one of 14 human P4-ATPases, is localized to endosomal compartments and the Golgi complex. In this study, we found that ATP9A is localized to phosphatidylserine (PS)-positive early and recycling endosomes, but not late endosomes, in HeLa cells. Depletion of ATP9A delayed the recycling of transferrin from endosomes to the plasma membrane, although it did not affect the morphology of endosomal structures. Moreover, depletion of ATP9A caused accumulation of glucose transporter 1 in endosomes, probably by inhibiting their recycling. By contrast, depletion of ATP9A affected neither the early/late endosomal transport and degradation of epidermal growth factor (EGF) nor the transport of Shiga toxin B fragment from early/recycling endosomes to the Golgi complex. Therefore ATP9A plays a crucial role in recycling from endosomes to the plasma membrane.
Journal Article γ-Adaptin Interacts Directly with Rabaptin-5 through Its Ear Domain1 Get access Yoko Shiba, Yoko Shiba Institute of Biological Sciences and Gene Research Center, University of TsukubaTsukuba Science City, Ibaraki 305-8572 Search for other works by this author on: Oxford Academic PubMed Google Scholar Hiroyuki Takatsu, Hiroyuki Takatsu Institute of Biological Sciences and Gene Research Center, University of TsukubaTsukuba Science City, Ibaraki 305-8572 Search for other works by this author on: Oxford Academic PubMed Google Scholar Hye-Won Shin, Hye-Won Shin 4 Institute of Biological Sciences and Gene Research Center, University of TsukubaTsukuba Science City, Ibaraki 305-8572 4 Present address: Max Planck Institute for Molecular Cell Biology and Genetics, 01307 Dresden, Germany. Search for other works by this author on: Oxford Academic PubMed Google Scholar Kazuhisa Nakayama Kazuhisa Nakayama Institute of Biological Sciences and Gene Research Center, University of TsukubaTsukuba Science City, Ibaraki 305-8572 Search for other works by this author on: Oxford Academic PubMed Google Scholar The Journal of Biochemistry, Volume 131, Issue 3, March 2002, Pages 327–336, https://doi.org/10.1093/oxfordjournals.jbchem.a003107 Published: 01 March 2002 Article history Received: 21 November 2001 Accepted: 04 December 2001 Published: 01 March 2002
Background: Long-standing vigorous exercise may be associated with atrial structural remodelling.This remodelling process may be the cause of increased frequency of atrial arrythmias in athletes.Early diagnosis of atrial remodelling by atrial imaging has a key role in management of atrial arrythmias in elite athletes.Purpose: We aimed to detect early phases of atrial remodelling in elite athletes by 3D echo and serum markers of fibrosis.Methods: In this study, we enrolled weigth lifters (n=33), marathoners (n=32), sedantary participants (n=30) and patients who recieved cardiotoxic chemotheraphy (n=10).Serum TGF-beta levels were measured.Both left atrial (LA) 3D volume and strain values were analysed.Results: There was a positive correlation between serum TGF-beta levels and LA volumes and negative correlation between TGF-beta levels and strain values.TGF-beta levels were higher among chemotheraphy and weight lifter groups, compared to control and marathoner groups [mean 0,57±0,3 and0,55±0,2 vs 0,45±0,2 and0,47±0,2, respectively, p=0.005].LA volumes were higher among chemotheraphy and weight lifter groups [median 33 (26-38) and31 (23-36) respectiely, p=0,005], and strain values were lower in these two groups [mean 20,3±2,5 and 24,6±4,5, respectively, p<0,005] compared to control and marathoner groups (Table 1).Total exercise volume was higher in weight lifter group than marathoners (p=0,001).There wasn't any differance between all groups regarding left vetricular systolic and diastolic functions.
Rab11 family interacting protein 3/arfophilin‐1 is a dual effector of Rab11 and Arf6 and exhibits Rab11‐dependent localization to recycling endosomes in interphase. Furthermore, FIP3 undergoes dynamic redistribution to the intercellular bridge during cytokinesis. However, regulation of FIP3 redistribution and its local function by Rab11 and Arf6 has remained controversial. In this study, we developed a procedure for detecting endogenous FIP3, Arf6, and Rab11 and determined that FIP3 is localized near the intercellular bridge during cytokinesis, and to the Flemming body (the midbody) immediately before abscission; Rab11 is localized near the intercellular bridge, but not to the Flemming body; and Arf6 is localized to the Flemming body. Time‐lapse analyses showed that FIP3 is transported to the intercellular bridge during cytokinesis, together with Rab11; before abscission, FIP3 becomes localized to the Flemming body, where Arf6 is already present. After abscission, FIP3 and Arf6 are incorporated into one of the daughter cells as a Flemming body remnant. Based on these observations, we propose that FIP3 localization to recycling endosomes in interphase and their transport to the intercellular bridge during cytokinesis depend on Rab11, and targeting of FIP3‐positive endosomal vesicles to the Flemming body in the abscission phase depends on Arf6.
ABSTRACT Type IV P-type ATPases (P4-ATPases) serve as lipid flippases, translocating membrane lipids from the exoplasmic (or luminal) leaflet to the cytoplasmic leaflet of lipid bilayers. In mammals, these P4-ATPases are localized to distinct subcellular compartments. ATP8A1 and ATP9A, both members of the P4-ATPase family, are involved in endosome-mediated membrane trafficking, although the roles of P4-ATPases in the secretory pathway remain to be clarified. ATP9A and ATP9B are located in the trans -Golgi network, with ATP9A also present in endosomal compartments. This study unveiled the overlapping roles of ATP9A and ATP9B in transporting VSVG from the Golgi to the plasma membrane within the secretory pathway. Furthermore, we demonstrated that the flippase activities of ATP9A and ATP9B were crucial for transport process. Notably, we discovered the formation of homomeric and/or heteromeric complexes between ATP9A and ATP9B. The existence of the heteromeric complex notably contributed to the retention of ATP9A in the Golgi. Therefore, ATP9A and ATP9B play a role in the secretory pathway from the Golgi to the plasma membrane, forming either homomeric or heteromeric complexes.
