The ESCRT regulator Did2 maintains the balance between long-distance endosomal transport and endocytic trafficking

Abstract

In highly polarised cells, like fungal hyphae, early endosomes function in both endocytosis as well as long-distance transport of various cargo including mRNA and protein complexes. However, knowledge on the crosstalk between these seemingly different trafficking processes is scarce. Here, we demonstrate that the ESCRT regulator Did2 coordinates endosomal transport in fungal hyphae of Ustilago maydis. Loss of Did2 results in defective vacuolar targeting, less processive long-distance transport and abnormal shuttling of early endosomes. Importantly, the late endosomal protein Rab7 and vacuolar protease Prc1 exhibit increased shuttling on these aberrant endosomes suggesting defects in endosomal maturation and identity. Consistently, molecular motors fail to attach efficiently explaining the disturbed processive movement. Furthermore, the endosomal mRNP linker protein Upa1 is hardly present on endosomes resulting in defects in long-distance mRNA transport. In conclusion, the ESCRT regulator Did2 coordinates precise maturation of endosomes and thus provides the correct membrane identity for efficient endosomal long-distance transport.

mRNA transport in fungal top models

“…This caused defects in endosomal mRNA transport. Thus, the ESCRT regulator Did2 coordinates the two seemingly separate functions of early endosomes, long‐distance transport and endocytic trafficking . In line with these findings, in higher eukaryotes Rab5‐positive endosomes are involved in axonal growth and the ESCRT‐II complex participates in neuronal mRNA transport …”

“…A recent study answered the question how the Rrm4‐dependent special functions of early endosomes are linked to their classic function in endocytic trafficking, namely the internalization of plasma membrane proteins for degradation via late endosomes and vacuole/lysosomes . 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 . The latter mutant phenotype was due to disturbed endosomal maturation.…”

Fungal Morphogenesis, from the Polarized Growth of Hyphae to Complex Reproduction and Infection Structures

“…Minus-end-directed transport is conducted by cytoplasmic dynein, whose activity is regulated by the dynactin and FHF complex (FTS/Hook/FHIP) (163). Whereas kinesin-3 contains a pleckstrin homology domain for interactions with endosomal lipids (166,167), components of the FHF complex interact with Rab5 to connect dynein to early endosomes (163,168).…”

“…The ESCRT (endosomal sorting complex required for transport) regulator Did2 plays an important role (167). In the absence of Did2, the maturation of early endosomes is disturbed, resulting in an altered lipid composition.…”

“…This causes the altered attachment of molecular motors as well as mRNA cargo. The resulting hyphae exhibit defects in Rrm4-dependent mRNA transport and septin filament formation and grow bipolarly (167). Thus, the ESCRT regulator appears to orchestrate endocytosis and long-distance transport of endosomes.…”