“…Within the assigned categories of the vesicles directed from ER to Golgi, our studies documented structure and contents of apical and basolateral transport vesicles which revealed that their membrane assembly is dependent on the SphNH 2 -and Cer-synthesizing ER -constitutive enzymes providing SPhL core for GSL and SM assembled in Golgi [45] [47] [50] [53] [60]. The challenge confronted here was to identify membrane markers that differentiate between SM-containing basolateral and endosomal vesicles that with other membrane constituents co-determine their divergent destination sites.…”
Restitution of the cell organelles and the membrane implicates serine palmitoyltransferase (SPT) in signal-specific and selective assembly of the transport vesicles. Here, we reveal that SPT, embedded in the outer leaflet (OL) of endoplasmic reticulum (ER), is engaged in the synthesis of ER transport vesicles that recondition cell organelles, and the inner leaflet (IL) SPT in the restitution of the cell membrane. The OL SPT impacts assembly of sphingomyelinase (SMase)-susceptible ER vesicles but not the SMase-resistant and sphingolipid (SPhL) core-carrying vesicles that refurbish the cell membrane. The investigation of the SPT-initiated differences in the placement of SPhL in vesicular membranes by utilizing ER depleted of OL SPT, allows us to conclude that the restitution of endosomal and lysosomal membranes is achieved with the involvement of OL SPT, whereas the IL SPT is involved in formation of the lipid core for glycosphingolipids (GSL) and sphingomyelin (SM) of the apical and basolateral cell membrane. These findings along with our previously published report (Slomiany and Slomiany, Advances in Biological Chemistry, 2013, 3, 275-287), provide a clear distinction between the processes that renovate cell membrane and its organelles from that of the endocytotic cell debridement, and show that vesicles are navigated to the specific organelles and the cell membrane by the biomembrane constituents programmed in ER.
“…Within the assigned categories of the vesicles directed from ER to Golgi, our studies documented structure and contents of apical and basolateral transport vesicles which revealed that their membrane assembly is dependent on the SphNH 2 -and Cer-synthesizing ER -constitutive enzymes providing SPhL core for GSL and SM assembled in Golgi [45] [47] [50] [53] [60]. The challenge confronted here was to identify membrane markers that differentiate between SM-containing basolateral and endosomal vesicles that with other membrane constituents co-determine their divergent destination sites.…”
Restitution of the cell organelles and the membrane implicates serine palmitoyltransferase (SPT) in signal-specific and selective assembly of the transport vesicles. Here, we reveal that SPT, embedded in the outer leaflet (OL) of endoplasmic reticulum (ER), is engaged in the synthesis of ER transport vesicles that recondition cell organelles, and the inner leaflet (IL) SPT in the restitution of the cell membrane. The OL SPT impacts assembly of sphingomyelinase (SMase)-susceptible ER vesicles but not the SMase-resistant and sphingolipid (SPhL) core-carrying vesicles that refurbish the cell membrane. The investigation of the SPT-initiated differences in the placement of SPhL in vesicular membranes by utilizing ER depleted of OL SPT, allows us to conclude that the restitution of endosomal and lysosomal membranes is achieved with the involvement of OL SPT, whereas the IL SPT is involved in formation of the lipid core for glycosphingolipids (GSL) and sphingomyelin (SM) of the apical and basolateral cell membrane. These findings along with our previously published report (Slomiany and Slomiany, Advances in Biological Chemistry, 2013, 3, 275-287), provide a clear distinction between the processes that renovate cell membrane and its organelles from that of the endocytotic cell debridement, and show that vesicles are navigated to the specific organelles and the cell membrane by the biomembrane constituents programmed in ER.
“…The hepatocytes ER-derived transport vesicles fuse with basolateral membrane contain PIPs but their membranes are devoid of glycosphingolipids and PI3P, and they do not fuse with gastric epithelial apical membrane. Compositional differences between lipids of ER membrane, apical and basolateral cell membranes [18][19][20] and en bloc intercalation of lipids and membrane protein into specific site of the cell membrane which is synchronized with apical or basolateral secretion [15][16][17] support the concept that transport vesicles are precisely fashioned in ER and delivered to the specific site for the precise membrane restitution and the cell function. The stereotypic view that cellular vesicles capture protein, discharge it and return for the next tour of transport [2] is insensitive to the functional relevance of the precise intercalation of membrane proteins within specific membrane lipids.…”
Section: Introductionmentioning
confidence: 97%
“…Our previously published studies of apical transport in gastric mucosal epithelial cells demonstrated synchrony in the assembly of transport vesicles membrane and synthesis of apoprotein (apomucin) cargo [18,19]. Gastric mucosal epithelium elaborates enormous quantity of glycoprotein (mucin) and requires just as large synthetic capacity to generate membranes for the vesicles to move the cargo from ER to Golgi and to the apical cell membrane.…”
The synthesis of endoplasmic reticulum (ER)-derived transport vesicles is dictated by the contents and derivation of the cellular cytosol. The ER transport vesicles synthesized in the presence of gastric epithelial cells cytosol are destined for en bloc fusion with apical epithelial membrane, whereas those generated in hepatocytes-derived cytosol are destined for en bloc fusion with basolateral membrane. Moreover, during assembly of the dominant fraction of the apical or basolateral transport vesicles, a substantial fraction of the vesicles is produced that fuses with endosomes, and the vesicles with still unknown destination that remain in cytosol. The process of ER vesicles synthesis is blocked by RNase treatment, whereas Golgi vesicles assembly is not affected. The experiments indicate that transport vesicles' membrane composition and fidelity of its construction is defined in ER. The process involves synchronous membrane lipid synthesis, cotranslational intercalation of integral membrane proteins and containment of the vesicular cargo.
“…Although several attempts to reconstitute ER-to-Golgi apparatus transport of Cer in cell-free and semi-intact cell systems have been made, the findings from these studies with in vitro systems have varied. Some investigators reached the conclusion that Cer transport does not require ATP or cytosol (7,8), whereas others argued that fusion of ER-derived transport vesicles enriched in Cer with the Golgi membrane requires cytosol (9). The contradictory results most likely reflect the fact that the nature of intracellular transport of long chain Cer for de novo SM synthesis in intact cells was little known at that time, so that it was difficult to test how accurately the in vitro systems mimicked Cer trafficking events occurring in intact cells.…”
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