Autophagy is a process delivering cytoplasmic components to lysosomes for degradation. Autophagy may, however, play a role in unconventional secretion of leaderless cytosolic proteins. How secretory autophagy diverges from degradative autophagy remains unclear. Here we show that in response to lysosomal damage, the prototypical cytosolic secretory autophagy cargo IL-1β is recognized by speciali...

Degradation of misfolded secretory proteins has long been assumed to occur in the lumen of the endoplasmic reticulum (ER). Recent evidence, however, suggests that such proteins are instead degraded by proteasomes in the cytosol, although it remains unclear how the proteins are transported out of the ER. Here we provide the first genetic evidence that Sec61p, the pore-forming subunit of the prot...

Phospholipid metabolism plays a central role in regulating vesicular traffic in the secretory pathway. In mammalian cells, activation of a Golgi-associated phospholipase D activity by ADP-ribosylation factor results in hydrolysis of phosphatidylcholine to phosphatidic acid (PA). This reaction has been proposed to stimulate nascent secretory vesicle budding from the trans-Golgi network. It is un...

Calsyntenins are members of the cadherin superfamily of cell adhesion molecules. They are present in postsynaptic membranes of excitatory neurons and in vesicles in transit to neuronal growth cones. In the current study, calsyntenin-1 (CST-1) and calsyntenin-3 (CST-3) were identified by mass spectrometric analysis (LC-MS/MS) of integral membrane proteins from highly enriched secretory granule p...

Ultrastructural and immunohistochemical studies of the small intestine are described in a Japanese patient with alpha heavy chain disease who had a history of colonic ulcers. Endoscopic examinations revealed multiple gastric erosion, duodenal ulcer, and a thickened, cobblestone-like pattern composed of small nodules in the duodenum and jejunum, which was similar in appearance to Crohn's disease...

The 80K (80 x 10(3) Mr) integral membrane protein, first described in the secretory granules of rat basophilic leukaemia (RBL) cells, is also localized to lysosomes in these cells. The protein displays the same distribution in natural killer lymphocytes (RNK-7), wherein it codistributes with cytolysin in secretory granules. In contrast, the protein is absent from the endocrine and exocrine secr...

Secretory lysosomes are lysosomes which are capable of undergoing regulated secretion in response to external stimuli. Many cells of the immune system use secretory lysosomes to release proteins involved in their specialised effector mechanisms. Precisely how lysosomal secretion is regulated in each of these cell types is now the study of much research as these mechanisms control the ability of...

Parasitoid wasps produce virulence factors that bear significant resemblance to viruses and have the ability to block host defense responses. The function of these virulence factors, produced predominantly in wasp venom glands, and the ways in which they interfere with host development and physiology remain mysterious. Here, we report the discovery of a specialized system of canals in venom gla...

Cell-free protein-synthesizing systems from Escherichia coli and wheat germ were compared for their capacity to support the translocation of secretory proteins across microsomal membranes derived from mammalian endoplasmic reticulum. Three different secretory proteins, two of bacterial and one of eucaryotic origin, were tested in this respect. In all three cases a contrast between the results i...