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.

Keywords: dynein; endosome; hitchhiking; kinesin; microtubule; peroxisome.

Figure 1. Mechanisms of Cargo Hitchhiking

(A) In U. maydis ribosome-associated mRNAs hitchhike on EEs. The RNA-binding protein (RBP) Rrm4 links the mRNA to the early endosome-binding protein, Upa1. Kinesin-3 and dynein/dynactin motors are recruited via the motor adaptor Hok1 (related to mammalian Hook3). (B) In both U. maydis and A. nidulans peroxisomes hitchhike on EEs. The endosome-interacting protein, PxdA, is required for peroxisome hitchhiking and may act as a tether between the two organelles. The putative peroxisome receptor for PxdA has not yet been identified. Kinesin-3 and dynein/dynactin motors are recruited via the motor adaptor Hok1/HookA. Although not depicted here, Hook associates with endosomes via a larger protein complex that contains the homologs of the fused toes (FTS) and fused toes and hook interacting protein (FHIP) proteins.

Figure I. Filamentous Fungi are Model Polarized Cells

(A) Ustilago maydis is a pathogenic fungus that causes corn smut. Before infection it switches from yeast-like growth to filamentous growth. Researchers in the transport field primarily study haploid U. maydis that have been induced (via activation of a transcription factor) to grow in the filamentous, unipolar form. (B) A. nidulans has been a model organism in the transport field since classical genetic screens identified several genes required for mitosis and nuclear positioning [79,84,85]. Most researchers in the field perform experiments on haploid hyphae. Both U. maydis and A. nidulans have uniformly polarized microtubules close to the hyphal tip; therefore the directionality of cargos and motors can easily be determined in this region. (C) Neurons also have highly polarized microtubule cytoskeletons, particularly in axons, where plus-ends are located at the axon terminus.