Hitchhiking Across Kingdoms: Cotransport of Cargos in Fungal, Animal, and Plant Cells

Abstract

Eukaryotic cells across the tree of life organize their subcellular components via intracellular transport mechanisms. In canonical transport, myosin, kinesin, and dynein motor proteins interact with cargos via adaptor proteins and move along filamentous actin or microtubule tracks. In contrast to this canonical mode, hitchhiking is a newly discovered mode of intracellular transport in which a cargo attaches itself to an already-motile cargo rather than directly associating with a motor protein itself. Many cargos including messenger RNAs, protein complexes, and organelles hitchhike on membrane-bound cargos. Hitchhiking-like behaviors have been shown to impact cellular processes including local protein translation, long-distance signaling, and organelle network reorganization. Here, we review instances of cargo hitchhiking in fungal, animal, and plant cells and discuss the potential cellular and evolutionary importance of hitchhiking in these different contexts.

Keywords: cytoskeleton; dynein; hitchhiking; kinesin; motors; myosin.

Figure 1

Modes of intracellular transport. In cells, cargo is transported via direct or indirect association with motor proteins. (a) In canonical transport, cargos are associated with motor proteins via cargo adaptors. (Top) In microtubule-based transport, activating adaptors link dynein/dynactin to cargo adaptors. Kinesin tail domains can interact directly or indirectly with cargo adaptors. (Bottom) In actin-based transport, myosin tail domains interact with cargo adaptors. (b) In cytoplasmic streaming, primary cargos (numbered 1) are transported via canonical transport. Secondary cargos (numbered 2) are cotransported via hydrodynamic flow, which results from cytoplasmic movement generated by canonically transported cargos. (c) In hitchhiking, primary cargos are transported via canonical transport, while secondary cargos are cotransported by directly associating with primary cargos via hitchhiking adaptor proteins.

Figure 2

Messenger RNA hitchhiking in the budding yeast, Saccharomyces cerevisiae. (a) Two potential mechanisms for messenger RNA (mRNA) transport via She-dependent mechanisms in budding yeast. (Top) The myosin-V motor Myo4p transports mRNA on actin cables via a canonical transport mechanism. Myo4p associates directly with the cargo adaptor She3p, which forms a complex with mRNA-bound She2p. (Bottom) Myo4p transports mRNA via hitchhiking on the endoplasmic reticulum (ER). Myo4p associates with the ER cargo adaptor She3p. mRNA associates with the ER via the hitchhiking adaptor She2p. (b) A potential model for mRNA movement via hitchhiking is on coatomer-coated vesicles called COPI vesicles in budding yeast. The myosin-V motor Myo2p associates with COPI vesicles via an unknown cargo adaptor. Arf1p, coatomer, Pab1p, and mRNA form a complex on the surface of COPI vesicles, resulting in mRNA cotransport with COPI vesicles.

Figure 3

Messenger RNA hitchhiking in fungal hyphae. (a) In the hyphae of Candida albicans, SEC2 messenger RNA (mRNA) hitchhikes on secretory vesicles. Secretory vesicles are transported by the myosin-V motor Myo2p via an unknown cargo adaptor. The encoded protein of SEC2 mRNA, Sec2p, acts as a hitchhiking adaptor for SEC2 mRNA. (b) In the hyphae of Ustilago maydis, many mRNAs, including mRNA encoding cdc3 and its associated ribosomes, hitchhike on early endosomes. Early endosomes associate with dynein/dynactin and kinesin motors via the activating adaptor Hok1 in complex with the cargo adaptors Fts1 and Fhp1. A hitchhiking adaptor complex composed of Rrm4, Upa1, Upa2, and Pab1 links mRNA to early endosomes for cotransport.

Figure 4

Organelle hitchhiking in filamentous fungi. (a) In Ustilago maydis hyphae, endoplasmic reticulum (ER), lipid droplets, and peroxisomes hitchhike on early endosomes, but the tethers mediating those interactions are unknown. Early endosomes are transported bidirectionally via the Fts1-Hok1-Fhp1 complex, which associates with dynein/dynactin and kinesin-3. (b) In Aspergillus nidulans hyphae, peroxisomes hitchhike on early endosomes via the putative hitchhiking adaptors peroxisome distribution mutant A (PxdA) and DipA. Early endosomes are transported bidirectionally. Dynein/dynactin interacts with early endosomes via the FtsA-HookA-FHIPA complex. How kinesin-3 interacts with early endosomes and whether this interaction involves the FtsA-HookA-FHIPA complex are unknown.

Figure 5

Messenger RNA hitchhiking in neurons. (a) Early endosomes, lysosomes, and mitochondria in axons are transported long distances on microtubules. Messenger RNAs (mRNAs) hitchhike on these organelles by several mechanisms. (b) The five-subunit endosomal Rab5 and RNA/ribosome intermediary (FERRY) complex links many mRNAs and their associated ribosomes to early endosomes via a direct interaction between the FERRY complex component Fy-2 and Rab5. Rab5 also links dynein/dynactin to early endosomes via a direct interaction with FHIP1B, in complex with Fts and Hook1 or Hook3. (c) RNA granules hitchhike on lysosomes via ANXA11. Precursor microRNAs (pre-miRNAs) also hitchhike on lysosomes via an unknown tether. (d) Pink1 mRNA and associated ribosomes hitchhike on mitochondria via two mechanisms. Pink1 mRNA is translated while associated with mitochondria, and the translated mitochondrial targeting sequence (MTS) associates with the mitochondria, linking the mRNA beginning to be translated and its associated ribosomes to the mitochondria as well. Pink1 mRNA associates with synaptojanin-2 (SYNJ2), which binds mitochondria-associated synaptojanin 2–binding protein (SYNJ2BP). Mitochondria are transported via dynein/dynactin and kinesin-1 via the TRAK adaptor and Miro GTPase.

Figure 6

Potential instances of endoplasmic reticulum–endosome hitchhiking in animal cells. (a) The endoplasmic reticulum (ER) hitchhikes on late endosomes. The ER-associated VAMP-associated protein (VAP) interacts with ORP1L on late endosomes. ORP1L interacts with the surface of late endosomes as well as with Rab7. Rab7 also links late endosomes to dynein/dynactin via RILP. (b) The ER hitchhikes on kinesin-1-transported lysosomes via an unknown tether. Kinesin-1 is associated with lysosomes via Arl8b and SKIP. (c) The ER-associated protein Protrudin links the ER to late endosomes by binding lipids on the surface of late endosomes and Rab7. Protrudin also binds the kinesin-1 heavy chain and facilitates the transfer of kinesin-1 to FYCO1 present on late endosomes. FYCO1 then mediates the kinesin-1-dependent transport of late endosomes.

Figure 7

Messenger RNA hitchhiking in plant cells. (a) In the endosperm of the rice Oryza sativa, messenger RNAs (mRNAs) encoding the storage proteins glutelin and prolamine hitchhike on endosomes on the way to the endoplasmic reticulum (ER). The RNA-binding proteins RBP-P and RBP-L bind these mRNAs and associate with N-ethylmaleimide-sensitive factor (NSF), which binds Rab5a on the surface of endosomes. These endosomes require actin for their movement, potentially via a myosin motor. (b) In Arabidopsis thaliana, FLOWERING LOCUS T mRNA hitchhikes on multivesicular bodies to the plasmodesmata. FLOWERING LOCUS T mRNA directly associates with a member of the rotamase cyclophilin (ROC) family of proteins on the surface of multivesicular bodies. The long-distance transport of FLOWERING LOCUS T mRNA also requires actin and is potentially transported via a myosin motor. Anchoring of ROC mRNA at the plasmodesmata requires microtubules.

Figure 8

Potential instances of organelle hitchhiking in plant cells. (a) Myosin XI-K associates with the MyoB receptor on the surface of vesicles resembling beads on a string. MyoB vesicles have been implicated in the transport of multiple cargos by an unclear mechanism. Other cargos may hitchhike on MyoB vesicles via (left) a direct, sustained interaction or (middle) transient interactions. Alternatively, other cargos may move by (right) cytoplasmic streaming generated from the transport of MyoB vesicles. (b) The endoplasmic reticulum (ER) directly interacts with Golgi bodies via AtCASP. The coiled-coil region of AtCASP is required for this interaction. A myosin motor associated with either the ER or Golgi body may be involved in this hitchhiking. (c) Peroxisomes are cotransported with plastids such as chloroplasts. The peroxin Pex10 is required for this cotransport. Plastid movement is dependent upon the actin cytoskeleton and potentially a myosin motor. The actin cytoskeleton also influences peroxisome movement and its contact with plastids.