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JIP4 and RILPL1 utilize opposing motor force to dynamically regulate lysosomal tubulation

4 months 1 week ago
Lysosomes are dynamic organelles that remodel their membrane in response to stimuli. We previously uncovered a process we term LYsosomal Tubulation/sorting driven by LRRK2 (LYTL), wherein damaged lysosomes generate tubules sorted into vesicles. LYTL is orchestrated by the Parkinson's disease kinase LRRK2 that recruits the motor adaptor protein and RHD family member JIP4 to lysosomes. JIP4 enhances LYTL tubule extension toward the plus-end of microtubules. To identify new players involved in...
Luis Bonet-Ponce

Tau Axonal Sorting and Interaction With Synaptic Plasticity Modulators Is Domain- and Isoform-Dependent in Human iPSC-Derived Neurons

4 months 1 week ago
Somatodendritic missorting of the axonal microtubule-associated protein Tau is an early hallmark of Alzheimer's disease (AD) and other tauopathies. Tau missorting causes synaptic loss and neuronal dysfunction, but the mechanisms underlying both normal axonal sorting and pathological missorting remain unclear. The six human brain Tau isoforms show different axodendritic distribution, but the Tau domains governing intracellular sorting and essential interactors are unknown. Here, we aimed to...
Michael Bell-Simons

Vacuolar pH regulates clathrin-mediated endocytosis through TORC1 signaling during replicative aging

4 months 1 week ago
Clathrin-mediated endocytosis (CME) is a critical cellular process that regulates nutrient uptake, membrane composition, and signaling. Although replicative aging affects many cellular functions, its impact on CME remains largely unknown. We show that in budding yeast, older cells have slower assembly of early and coat CME modules, resulting in longer endocytic turnover and reduced Mup1 internalization. This change in CME dynamics is mother cell-specific, and not observed in daughters. Our data...
Kenneth Gabriel Antenor

Air pollution and impulsive choice in aging: evidence from delay discounting

4 months 1 week ago
Heightened air pollution exposure is associated with an increased risk for developing neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease, yet it is unclear how pollution impacts the aging brain more broadly. Rodent research has shown that higher air pollution exposure is associated with increased impulsive behavior, operationalized as a preference for immediate reward in delay discounting tasks. We examined this relationship in middle-aged and older humans by...
Maya R Kilcullen