ACBD5 and VAPB mediate membrane associations between peroxisomes and the ER

This is the final version of the article. Available from the publisher via the DOI in this record.Peroxisomes (POs) and the endoplasmic reticulum (ER) cooperate in cellular lipid metabolism and form tight structural associations, which were first observed in ultrastructural studies decades ago. PO–ER associations have been suggested to impact on a diverse number of physiological processes, including lipid metabolism, phospholipid exchange, metabolite transport, signaling, and PO biogenesis. Despite their fundamental importance to cell metabolism, the mechanisms by which regions of the ER become tethered to POs are unknown, in particular in mammalian cells. Here, we identify the PO membrane protein acyl-coenzyme A–binding domain protein 5 (ACBD5) as a binding partner for the resident ER protein vesicle-associated membrane protein-associated protein B (VAPB). We show that ACBD5–VAPB interaction regulates PO–ER associations. Moreover, we demonstrate that loss of PO–ER association perturbs PO membrane expansion and increases PO movement. Our findings reveal the first molecular mechanism for establishing PO–ER associations in mammalian cells and report a new function for ACBD5 in PO–ER tethering.This work was supported by grants from the Biotechnology and Biological Sciences Research Council (BB/K006231/1 and BB/ N01541X/1 to M. Schrader). J. Metz and M. Schrader are supported by a Wellcome Trust Institutional Strategic Support Award (WT097835MF and WT105618MA) and L.F. Godinho by a fellowship from Fundação para a Ciência e a Tecnologia, Portugal (SFRH/ BPD/90084/2012). M. Schrader and A.S. Azadi are supported by Marie Curie Initial Training Network action PerFuMe (316723). M. Islinger is supported by MEAMEDMA Anschubförderung, Medical Faculty Mannheim, University of Heidelberg

Multilevel Modeling of Gaze From Listeners With Hearing Loss Following a Realistic Conversation

Purpose: There is a need for tools to study real-world communication abilities in people with hearing loss. We outline a potential method for this that analyzes gaze and use it to answer the question of when and how much listeners with hearing loss look toward a new talker in a conversation. Method: Twenty-two older adults with hearing loss followed a prerecorded two-person audiovisual conversation in the presence of babble noise. We compared their eye-gaze direction to the conversation in two multilevel logistic regression (MLR) analyses. First, we split the conversation into events classified by the number of active talkers within a turn or a transition, and we tested if these predicted the listener’s gaze. Second, we mapped the odds that a listener gazed toward a new talker over time during a conversation transition. Results: We found no evidence that our conversation events predicted changes in the listener’s gaze, but the listener’s gaze toward the new talker during a silence-transition was predicted by time: The odds of looking at the new talker increased in an s-shaped curve from at least 0.4 s before to 1 s after the onset of the new talker’s speech. A comparison of models with different random effects indicated that more variance was explained by differences between individual conversation events than by differences between individual listeners. Conclusions: MLR modeling of eye-gaze during talker transitions is a promising approach to study a listener’s perception of realistic conversation. Our experience provides insight to guide future research with this method.</p