Hitchhiking: A Non-Canonical Mode of Microtubule-Based Transport

Abstract

The long-range movement of organelles, vesicles, and macromolecular complexes by microtubule-based transport is crucial for cell growth and survival. The canonical view of intracellular transport is that each cargo directly recruits molecular motors via cargo-specific adaptor molecules. Recently, a new paradigm called ‘hitchhiking’ has emerged: some cargos can achieve motility by interacting with other cargos that have already recruited molecular motors. In this way, cargos are co-transported together and their movements are directly coupled. Cargo hitchhiking was discovered in fungi. However, the observation that organelle dynamics are coupled in mammalian cells suggests that this paradigm may be evolutionarily conserved. We review here the data for hitchhiking and discuss the biological significance of this non-canonical mode of microtubule-based transport.

mRNA transport in fungal top models

“…103 Thus, it appears to be a common theme that specific adaptor proteins are needed to direct individual cargoes like mRNPs or peroxisomes to early endosomes for long-distance transport. 78 A recent study answered the question how the Rrm4-dependent special functions of early endosomes are linked to their classic function in endocytic trafficking, 104 namely the internalization of plasma membrane proteins for degradation via late endosomes and vacuole/lysosomes. 105 Loss of the crucial ESCRT regulator Did2 in U. maydis resulted in defective vacuolar targeting of proteins as well as in altered unipolar growth, resembling mutants affected in microtubule function.…”

Dynein binds and stimulates axonal motility of the endosome adaptor and NEEP21 family member, calcyon

“…At minus ends, Lis1 facilitates the loading of dynein onto kinesin-positive organelles for transport to plus ends (Taya et al, 2007; Yamada et al, 2008). Thus, Lis1-related alterations in Caly anterograde movement could reflect an indirect ‘hitchhiking’ effect by virtue of the ability of Caly to bind directly to IC (Salogiannis and Reck-Peterson, 2016). …”

Symposium review: Intravital imaging of the lactating mammary gland in live mice reveals novel aspects of milk-lipid secretion

“…This mechanism may also explain the slow and intermittent nature of lipid droplet movement and would be compatible with transit-associated fusions, provided that droplets are still able to contact each other across the gap between adjacent vesicles. Such "hitchhiking" mechanisms have recently been identified in other systems, including the transport of lipid droplets, endoplasmic reticulum elements, and peroxisomes in fungal hyphae (Salogiannis and Reck-Peterson, 2017).…”

“…Lipid droplets have been implicated in protein trafficking, lipid signaling pathways, and the sequestration of misfolded proteins, and they play contradictory roles as platforms for both the assembly of viral particles and as reservoirs of antiviral and antibacterial proteins. In line with such multifunctional roles, lipid droplets associate with other organelles besides the rER, including mitochondria, peroxisomes, the Golgi complex, and elements of the endosomal pathway (Martin et al, 2005;Barbosa et al, 2015;Salogiannis and Reck-Peterson, 2017;Valm et al, 2017). However, despite such inter-organellar interactions, many lipid droplets may never leave the rER but remain attached to the cytoplasmic face of the membrane.…”