Biology subjects

Drerup, C. M.

Publications and source records attributed to Drerup, C. M..

3 recordsLinked to original sources

bioRxiv2020

Vezatin is required for the retrograde axonal transport of endosomes in Drosophila and zebrafish

Active transport of organelles within axons is critical for neuronal health. Retrograde axonal transport, in particular, relays neurotrophic signals received by axon terminals to the nucleus and circulates new material among en passant synapses. The single retrograde motor, cytoplasmic dynein, is linked to diverse cargos by adaptors that promote dynein motility. Here we identify Vezatin as a new, cargo-specific regulator of retrograde axonal transport. Loss-of-function mutations in the Drosophila vezatin-like (vezl) gene prevent signaling endosomes containing activated BMP receptors from initiating transport out of motor neuron terminal boutons. vezl loss also decreases the transport of endosomes and dense core vesicles (DCVs) within axon shafts. While vertebrate Vezatin (Vezt) has not previously been implicated in axonal transport, we show that vezt loss in zebrafish impairs the retrograde movement of late endosomes, causing their accumulation in axon terminals. Our work establishes a new, conserved, cargo-specific role for Vezatin proteins in axonal transport.

cell biology↗

bioRxiv2019

Retrograde mitochondrial transport is essential for mitochondrial homeostasis in neurons

Mitochondrial transport in neurons is essential for forming and maintaining axonal projections. While much is known about anterograde mitochondrial movement, the function of retrograde mitochondrial motility in neurons was unknown. We investigated the dynamics and utility of retrograde mitochondrial transport. Using long-term tracking of mitochondria in vivo, we found mitochondria in axon terminals turnover within hours via retrograde transport. Mitochondria do not return to the cell body solely for degradation; rather, mitochondria use bidirectional transport to redistribute themselves throughout the neuron. Disruption of retrograde mitochondrial transport severely depletes the cell body of mitochondria and impacts mitochondrial health throughout the cell. Altered mitochondrial health correlates with decreased synaptic activity. Using proteomics, we provide evidence that retrograde mitochondrial movement functions to maintain the organelles proteome. Together, our work demonstrates that mitochondrial retrograde transport is essential for the maintenance of a homeostatic population of mitochondria in neurons and consequently effective synaptic activity through promoting mitochondrial protein turnover.

neuroscience↗

bioRxiv2018

A specific Ret receptor isoform is required for pioneer axon outgrowth and growth cone dynamics

In many cases, axon growth and guidance are driven by pioneer axons, the first axons to grow in a particular region. Despite their dynamic pathfinding capabilities and developmental importance, there are very few pioneer neuron specific markers and thus their in vivo identification and functional interrogation have been difficult. We found that a Ret receptor isoform, Ret51, is highly enriched in peripheral sensory pioneer neurons and is required for pioneer axon outgrowth. Ret null mutant pioneer neurons differentiate normally; however, they displayed defects in growth cone morphology and formation of filopodia before pioneer axon extension prematurely halts. We also demonstrate loss-of-function of a retrograde cargo adaptor, JNK-interacting protein 3 (Jip3), phenocopied many of these axonal defects. We further found that loss of Jip3 led to accumulation of activated Ret receptor in pioneer growth cones, indicating a failure in the clearance of activated Ret from growth cones. Using an axon sever approach as well as in vivo analysis of axonal transport, we showed Jip3 specifically mediates retrograde, but not anterograde, transport of activated Ret51. Finally, live imaging revealed that Jip3 and Ret51 were retrogradely co-transported in pioneer axons, suggesting Jip3 functions as an adapter for retrograde transport of Ret51. Taken together, these results identify Ret51 as a molecular marker of pioneer neurons and elucidate an important isoform-specific role for Ret51 in axon growth and growth cone dynamics during development.

developmental biology↗