ATP-dependent membrane transport

Schrickx J, Lektarau Y, Fink-Gremmels J (2006) Ochratoxin A secretion by ATP-dependent membrane transporters in Caco-2 cells. Arch Toxicol 80 243-249. 

The adenylyl cyclases are large transmembrane proteins with a complex transmembrane topology. The assumed topology (Fig. 5.22) shows a short cytoplasmic N-termi-nal section followed by a transmembrane domain Ml with six transmembrane sections, and a large cytoplasmic domain Cl. The structural motif is repeated so that a second transmembrane domain M2 and a second cytoplasmic domain C2 can be differentiated. The complicated structure resembles the structure of some ATP-dependent membrane transport systems such as the P glycoprotein. A transport function has not yet been demonstrated for adenylyl cyclase. 

Prishchepa LA, Burdyga TV, Kosterin SA 1996 Two components of sodium azide-insensitive Mg2+, ATP-dependent Ca2+ transport in ureteral smooth muscle membrane structures (translated from Russian). Biokhimiia 61 1250—1256 Rose JG, Gillenwater JY 1973 Pathophysiology of ureteral obstruction. Am J Physiol 225 830-837... 

Some cells couple the pure transport forms discussed on p. 218—i.e., passive transport (1) and active transport (2)—and use this mechanism to take up metabolites. In secondary active transport (3), which is used for example by epithelial cells in the small intestine and kidney to take up glucose and amino acids, there is a symport (S) located on the luminal side of the membrane, which takes up the metabolite M together with an Na" ion. An ATP-dependent Na transporter (Na /lC ATPase see p. 350) on the other side keeps the intracellular Na+ concentration low and thus indirectly drives the uptake of M. Finally, a uniport (U) releases M into the blood. 

Note Plasma membrane vesicles were either isolated from roots previously treated with HS4 and then assayed for the ATP-hydrolyzing activity or isolated from untreated roots and then incubated directly in the assay medium with IIS for the measurement of the scalar (ATP hydrolysis) and vectorial (ATP-dependent H+ transport) activity. 

Glucagon causes a 30-40% inhibition of ATP-dependent Ca2+ transport activity and (Ca2+-Mg2+)-ATPase activity in liver plasma membranes [150-152]. however, much higher glucagon concentrations (0.1-10/i.M) are required to produce these changes [150-152] than to activate adenylate cyclase (0.1-100 nM), and the inhibition of the ATPase is not mimicked by cAMP or its analogues [157]. The effects of several glucagon derivatives on the ATPase are also very different from their effects on adenylate cyclase [150]. All of these observations indicate that the two effects are not related. 

One of the popular experimental systems to investigate the hepatic efflux process is canalicular membrane vesicle (CMV). It is difficult to evaluate the transport activity of efflux transporters in cell systems because substrates cannot easily access the intracellular compartment, so CMV system is often used to rapidly determine the ATP-dependent efflux transport of substrates across bile canalicular membrane. 

The results indicate that the initial rate of transport of PE is rapid and proceeds without a lag (Fig. 8). The transport process is insensitive to metabolic poisons that disrupt vesicle transport and cytoskeletal structure. The rapid transport kinetics occur at rates consistent with a soluble carrier-mediated process or transfer at zones of apposition between membranes. Analysis of the kinetics of the process is complicated since only PE at the outer leaflet of the plasma membrane is measured, and the basal scramblase activity or the leakage of the ATP-dependent aminophospholipid transporter activity within the plasma membrane may be a step required for the lipid to arrive at this location. Despite these complications, the results clearly indicate that the initial rate of arrival of PE at the plasma membrane occurs on a timescale that clearly distinguishes it from well-characterized vesicle transport phenomena, and is independent of processes involved in protein transport to the cell surface. 

Olbe M and Sommarin M (1991) ATP-dependent Ca transport in wheat root plasma membrane vesicles. Physiol Plant 83 535-543. 

Ghijsen (1982) la,25-Dihydroxyvitamin D regulates ATP-dependent calcium transport in basolat-eral plasma membranes of rat enterocytes. Biochim Biophys Acta 689 170-172. 

Adachi Y, Kobayashi H, Kurumi Y, Shouji M, Kitano M, Yamamoto T. ATP-dependent taurocholate transport by rat liver canalicular membrane vesicles. Hepatology (Philadelphia, PA, United States) 1991 14 655-659. 

Among all ABC transporters, P-gp, also known as MDRl protein, ABCBl or CD243, is probably the most studied and characterized member. It was first found as a 170-kDa ATP-dependent membrane glycoprotein that acts as a drug efflux pump [15], P-gp is a broad-spectrum transporter, capable of transporting several structurally and functionally unrelated substrate molecules. Its substrates are typically hydrophobic, amphipathic products, including many chemotherapeutic compounds used for cancer treatment, e.g., vinca alkaloids (vincristine, vinblastine), taxanes (paclitaxel, docetaxel), epipodophyllotoxins (etoposide, teniposide), anthracyclines (doxorubicin, daunorubicin, epirubicin), topotecan, dactinomycin, and mitomycin-C [37]. 

Fig. 2. Requirements of transport to recycling endosomes in vitro. (A) After immunoisolation of acceptor recycling endosomes using beads coated with anti-Rabll-antibodies (anti-Rabll) or with anti-rabbit antibodies (IgG control), beads were incubated with donor endosomes for 30 min at 37°. Only for anti-Rabll-isolated membranes efficient transfer of Ac-Tfn was detected, thus excluding unspecific binding of labeled endosomes to magnetic beads. (B) Incubation of anti-Rabll isolated acceptor membranes with donor endosomes for 30 min at 37° or 4° demonstrates the temperature-dependency of transport to recycling endosomes. (C) Acceptor membranes immunoisolated with anti-Rabll were incubated for 30 min at 37° with donor endosomes in the presence of an ATP-regenerating system (control) or an ATP-depletion system (ATP-depletion). The approximately 50% inhibition after depletion of cytosolic ATP reflects the general requirement of ATP for membrane transport. Error bars represent the standard deviation of three experiments (reprinted from Biochemical and Biophysical Research Communications, Vol. 3 [Bartz et al., 2003]. 2003, with permission from Elsevier).

Tsai K-J, Linet AL (1993) Formation of a phosphorylated enzyme intermediate by the cadA Cd -ATPase. Arch Biochem Biophys 305 267-270 Tsai K-J, Yoon KP, Lynn AR (1992) ATP-dependent cadmium transport by the cadA cadmium resistance determinant in everted membrane vesicles of Bacillus subtilis. J Bacteriol 174 116-121... 

Lockau W and Pfeffer S (1982) A cyanobacterial ATPase distinct from the coupling factor of photophosphorylation, Z. Naturforsch. 35C, 558-554. Lockau W and Pfeffer S (1983) ATP-dependent calcium transport in membrane vesicles of the cyanobacterium, Anabaena variabilis, Biochim. Biophys. 

Proteins that can flip phospholipids from one side of a bilayer to the other have also been identified in several tissues (Figure 9.11). Called flippases, these proteins reduce the half-time for phospholipid movement across a membrane from 10 days or more to a few minutes or less. Some of these systems may operate passively, with no required input of energy, but passive transport alone cannot establish or maintain asymmetric transverse lipid distributions. However, rapid phospholipid movement from one monolayer to the other occurs in an ATP-dependent manner in erythrocytes. Energy-dependent lipid flippase activity may be responsible for the creation and maintenance of transverse lipid asymmetries. 

The ABC-transporter superfamily represents a large group of transmembrane proteins. Members of this family are mainly involved in ATP-dependent transport processes across cellular membranes. These proteins are of special interest from a pharmacological point of... 

The Ca transport ATPase of sarcoplasmic reticulum is an intrinsic membrane protein of 110 kDa [8-11] that controls the distribution of intracellular Ca by ATP-dependent translocation of Ca " ions from the cytoplasm into the lumen of the sarcoplasmic reticulum [12-16],... 

Our discussion here will concentrate on the various forms of the Ca " transport ATPases that occur in the sarcoplasmic reticulum of muscle cells of diverse fiber types and in the endoplasmic reticulum of nonmuscle cells (SERCA). The structure of these enzymes will be compared with the Ca transport ATPases of surface membranes (PMCA) [3,29-32,34] and with other ATP-dependent ion pumps that transport Na, K, andH [46,50-52]. 

Heijn, M., Oude Elferink, R. and Jansen, P. (1992). ATP-dependent multispecific organic anion transport system in rat erythrocyte membrane vesicles. Am. J. Physiol. 262, 104-110. 

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