Ion channels composed of pore-forming and auxiliary subunits control physiological functions in virtually all cell types. A conventional view is that channels assemble with their auxiliary subunits before anterograde plasma membrane trafficking of the protein complex. Whether the multisubunit composition of surface channels is fixed following protein synthesis or flexible and open to acute and,...

Plant vacuoles are versatile organelles critical for plant growth and responses to environment. Vacuolar proteins are transported from the endoplasmic reticulum via multiple routes in plants. Two classic routes bear great similarity to other phyla with major regulators known, such as COPII and Rab5 GTPases. By contrast, vacuolar trafficking mediated by adaptor protein-3 (AP-3) or that independe...

The components involved in cellular trafficking and protein recycling machinery that have been associated with increased Alzheimer's disease (AD) risk belong to the late secretory compartments for the most part. Here, we hypothesize that these late unavoidable events might be the consequence of earlier complications occurring while amyloid precursor protein (APP) is trafficking through the earl...

Ubiquitylation is a key regulator of protein trafficking, and much about the functions of ubiquitin ligases, which add ubiquitin to substrates in this regulation, has recently come to light. However, a clear understanding of ubiquitin-dependent protein localization cannot be achieved without knowledge of the role of deubiquitylating enzymes (DUBs). DUBs, by definition, function downstream in ub...

The Wilson protein (ATP7B) is a copper-transporting CPx-type ATPase defective in the copper toxicity disorder Wilson disease. In hepatocytes, ATP7B delivers copper to apo-ceruloplasmin and mediates the excretion of excess copper into bile. These distinct functions require the protein to localize at two different subcellular compartments. At the trans-Golgi network, ATP7B transports copper for i...

Endoplasmic reticulum (ER)–plasma membrane (PM) contact sites/junctions play important roles in cell physiology including signal transduction, ion and lipid transfer, dynamics. However, little is known about the dynamic regulation functional of ER–PM junctions neurons. Using a split green fluorescent protein-based probe, we find that density sites changes dynamically dendrites hippocampal neuro...

Abstract Bis‐ethynylphosphonamidates allow for a simple chemoselective addition of two thiol‐containing modules in row. We describe four such bis‐electrophiles that carry different functional O‐substituents with tunable hydrophilicity and enable further subsequent conjugations, thus facilitating protocol constructing protein‐protein conjugates. An increased spacer length between the ethynylphos...

Yeast Vps24p (vacuolar protein sorting) is part of a protein complex suggested to function in sorting/trafficking during endocytosis. We have characterized a mammalian homolog of the yeast protein, mVps24p, and examined its role in epidermal growth factor receptor trafficking. Endogenous mVps24p was distributed in both cytosol and in puncta and partially colocalized with markers for the trans-G...

More than 2 decades of work have yet to conclusively determine the physiological role of the synuclein proteins, even though these abundant brain constituents are participants in a broad array of cellular processes. Among proposed physiological roles is a functional interaction between the synuclein proteins and monoamine transporters contributing to transporter trafficking through direct prote...