Protein quality control machinery supports primary ciliogenesis by eliminating GDP-bound Rab8-family GTPases.

The small GTPase Rab8 plays a vital role in the vesicular trafficking of cargo proteins from the Golgi network to target membranes. Upon reaching its target destination, Rab8 is released from the vesicular membrane into the cytoplasm via guanosine triphosphate (GTP) hydrolysis. The fate of GDP-bound Rab8 released from the destination membranes, however, has not been investigated adequately.

Leishmania major Strain-Dependent Macrophage Activation Contributes to Pathogenicity in the Absence of Lymphocytes.

Infection of C57BL/6 wild-type mice with Leishmania major 5-ASKH or Friedlin strains results in relatively similar pathogenicity with self-healing lesions within weeks. Parasite clearance depends on nitric oxide production by activated macrophages in response to cytokines produced mainly by CD4 Th1 cells. In contrast, C57BL/6 Rag2 knockout mice, which lack T and B lymphocytes, show distinct pathologies during infection with these strains.

BAG6 deficiency induces mis-distribution of mitochondrial clusters under depolarization.

Accumulation of damaged mitochondria is implicated in a number of neurodegenerative disorders, including Parkinson's disease. Therefore, the machinery for mitochondrial quality control is important for the prevention of such diseases. It has been reported that Parkin- and p62/sequestosome 1 (SQSTM1)-mediated clustering and subsequent elimination of damaged mitochondria (termed mitophagy) are critical for maintaining the quality of mitochondria under stress induced by uncoupling agents such as carbonyl cyanide m-chlorophenyl hydrazone.

Elimination of a signal sequence-uncleaved form of defective HLA protein through BAG6.

A portion of newly synthesized transmembrane domain proteins tend to fail to assemble correctly in the lumen of the endoplasmic reticulum, thus resulting in the production of a signal sequence-uncleaved form of the defective species. Although the efficient degradation of these mistargeted polypeptides is crucial, the molecular mechanism of their elimination pathway has not been adequately characterized. In this study, we focused on one such cryptic portion of a defective transmembrane domain protein, HLA-A, and show that a part of HLA-A is produced as a signal sequence-uncleaved labile species that is immediately targeted to the degradation pathway.

A conserved island of BAG6/Scythe is related to ubiquitin domains and participates in short hydrophobicity recognition.

BAG6 (also called Scythe) interacts with the exposed hydrophobic regions of newly synthesized proteins and escorts them to the degradation machinery through mechanisms that remain to be elucidated. In this study, we provide evidence that BAG6 physically interacts with the model defective protein substrate CL1 in a manner that depends directly on its short hydrophobicity. We found that the N terminus of BAG6 contains an evolutionarily conserved island tentatively designated the BAG6 ubiquitin-linked domain.