RING finger protein 13 (RNF13) is a ubiquitously expressed, highly regu-lated ubiquitin ligase anchored in endosome membranes. A RING domain
located in the cytoplasmic half of this type 1 membrane protein mediates
ubiquitinationin vitro but physiological substrates have not yet been identi-fied.
The plasma membrane proteins CD1a, CD1b and CD1c are expressed by
human dendritic cells, the professional antigen-presenting cells of the
immune system, and present lipid antigens to T lymphocytes. CD1e
belongs to the same family of molecules, but accumulates as a membrane-associated form in the Golgi compartments of immature dendritic cells and
as a soluble cleaved form in the lysosomes of mature dendritic cells.
During cell intoxication by diphtheria toxin, endosome acidification trig-gers the translocation of the catalytic (C) domain into the cytoplasm. This
event is mediated by the translocation (T) domain of the toxin. Previous
work suggested that the T domain acts as a chaperone for the C domain
during membrane penetration of the toxin.
After fusion with the cellular plasma membrane or endosomal membranes,
viral particles are generally too large to diffuse freely within the crowded
cytoplasm environment. Thus, they will never reach the cell nucleus or the
perinuclear areas where replication or reverse transcription usually takes
During endocytic transport, specific integral membrane proteins are sorted
into intraluminal vesicles that bud from the limiting membrane of the
endosome. This process, known as multivesicular body (MVB) sorting, is
important for several important biological processes.
The endosomal compartment of the cell is involved in a number of func-tions including: (a) internalizing membrane proteins to multivesicular
bodies and lysosomes; (b) producing vesicles that are secreted from the cell
(exosomes); and (c) generating autophagic vesicles that, especially in times
of nutrient deprivation, supply cytoplasmic components to the lysosome
for degradation and recycling of nutrients.
The intracellular role of placental protein 17b (PP17b)/
TIP47has been controversial, because it is considered tobe a
protein required for mannose 6-phosphate receptor trans-port from endosome totrans-Golgi as well as a neutral lipid
droplet-associatedprotein.The similaritybetween theamino
acid sequences of PP17 variants, adipophilin and perilipins,
andbetween their gene structures indicate that PP17baswell
as other alternatively spliced PP17 variants belong to the
lipid storage droplet protein family, containing also some
Ever since their discovery adenoviruses have proven to be a
tremendous asset to biologists. Through the study of the adenoviruses,
we have learned not only about the virus structures, mechanisms of viral
replication, but also about eukaryotic gene expression, alternative splicing,
regulation of cell cycle progression, and apoptosis. In the last five years,
there has been an explosion in the use of adenoviruses as vectors for gene
transfer to a variety of mammalian cells.
Endocytic and biosynthetic trafficking pathways to the lysosome⁄vacuole
converge at the prevacuolar endosomal compartment. During transport
through this compartment, integral membrane proteins that are destined
for delivery to the lysosome⁄vacuole lumen undergo multivesicular body
(MVB) sorting into internal vesicles formed by invagination of the endo-somal limiting membrane.
PA-TM-RING proteins have an N-terminal protease-associated domain, a
structure found in numerous proteases and implicated in protein binding,
and C-terminal RING finger and PEST domains. Homologous proteins
include GRAIL (gene related to anergy in leukocytes), which controls
T-cell anergy, and AtRMR1 (receptor homology region-transmembrane
domain-RING-H2 motif protein), a plant protein storage vacuole sorting
Differential subcellular compartmentalization of the three main Ras
isoforms (H-Ras, N-Ras and K-Ras) is believed to underlie their biological
differences. Modulatable interactions between cellular membranes and Ras
C-terminal hypervariable region motifs determine differences in trafficking
and the relative proportions of each isoform in cell-surface signalling
nanoclusters and intracellular endoplasmic reticulum⁄Golgi, endosomal
and mitochondrial compartments.
Despite the critical importance of protein ubiquitination in the regulation
of diverse cellular processes, the molecular mechanisms by which cells rec-ognize and transmit ubiquitin signals remain poorly understood. The
endosomal sorting machinery component hepatocyte growth factor-regu-lated tyrosine kinase substrate (Hrs) contains a ubiquitin-interacting motif
(UIM), which is believed to bind ubiquitinated membrane cargo proteins
and mediate their sorting to the lysosomal degradation pathway.
Both Shiga holotoxin and the isolated B subunit, navigate a retrograde
pathway from the plasma membrane to the endoplasmic reticulum (ER) of
mammalian cells to deliver catalytic A subunits into the cytosol. This route
passes through early⁄recycling endosomes and then through the Golgi.
The Vps4 C-terminal helix is a critical determinant for assembly and ATPase activity and has elements conserved in other members of the meiotic clade of AAA ATPasesSorting of membrane proteins into intralumenal endosomal vesicles, mul-tivesicular body (MVB) sorting, is critical for receptor down regulation,
antigen presentation and enveloped virus budding. Vps4 is an AAA
ATPase that functions in MVB sorting. Although AAA ATPases are oligo-meric, mechanisms that govern Vps4 oligomerization and activity remain
Parimala R. Vajjhala1,2, Chau H. Nguyen1,2, Michael J.