Drive the Car(go)s—New Modalities to Control Cargo Trafficking in Live Cells

Abstract

Synaptic transmission is a fundamental molecular process underlying learning and memory. Successful synaptic transmission involves coupled interaction between electrical signals (action potentials) and chemical signals (neurotransmitters). Defective synaptic transmission has been reported in a variety of neurological disorders such as Autism and Alzheimer’s disease. A large variety of macromolecules and organelles are enriched near functional synapses. Although a portion of macromolecules can be produced locally at the synapse, a large number of synaptic components especially the membrane-bound receptors and peptide neurotransmitters require active transport machinery to reach their sites of action. This spatial relocation is mediated by energy-consuming, motor protein-driven cargo trafficking. Properly regulated cargo trafficking is of fundamental importance to neuronal functions, including synaptic transmission. In this review, we discuss the molecular machinery of cargo trafficking with emphasis on new experimental strategies that enable direct modulation of cargo trafficking in live cells. These strategies promise to provide insights into a quantitative understanding of cargo trafficking, which could lead to new intervention strategies for the treatment of neurological diseases.

Strategies for Conditional Regulation of Proteins

“…Decaging the lysine with 2-(diphenylphosphanyl)­benzamide localized the POI at the nuclear membrane through interactions with the nuclear pore complex . Magnetic control of proteins can also be achieved by conjugating or fusing the POI with an antibody-functionalized with superparamagnetic nanoparticles . Alternatively, a functionalized antibody can be directly used to bring together the POI in the cell through noncovalent interactions, whose localization can be controlled using an electromagnetic needle .…”

“… 172 Magnetic control of proteins can also be achieved by conjugating or fusing the POI with an antibody-functionalized with superparamagnetic nanoparticles. 173 Alternatively, a functionalized antibody can be directly used to bring together the POI in the cell through noncovalent interactions, whose localization can be controlled using an electromagnetic needle. 174 The anchor away system is another technique used to evacuate nuclear POIs conditionally and rapidly away from the nucleus using specific chemical stimuli to tether them in the cytoplasm resulting in their loss of function.…”

Trafficking mechanisms of synaptogenic cell adhesion molecules

“…The advent of cutting-edge in vivo live-cell imaging techniques and super-resolution microscopy (Villa et al, 2016;Zhang et al, 2015), in combination with systems that enable spatiotemporal control over cargo trafficking (Boncompain et al, 2012;Mondal et al, 2017), provide unparalleled opportunities to unravel the diversity of secretory routes and to decipher the trafficking pathways that govern synaptic targeting of CAMs. In addition, advances in proteomics (Loh et al, 2016;Uezu et al, 2016) and the ability to isolate distinct subcellular compartments (Drissi et al, 2013;Tharkeshwar et al, 2017) should allow for the identification of novel CAM-interacting proteins in a compartment-specific manner.…”

Chemical physics in living cells — Using light to visualize and control intracellular signal transduction

“…The recent DOI:10.1063/1674-0068/31/cjcp1806152 c ⃝2018 Chinese Physical Society evolution of optogenetic and optochemical systems has enabled perturbation at a level suitable for accomplishing these tasks. For a more elaborate discussion on these new experimental strategies for modulating cargo trafficking, we refer the readers to our recent review [126]. Here, we present a succinct discussion of recent optogenetic and optochemical approaches to achieving experimental cargo trafficking.…”