Biology subjects

Xiong, W.-C.

Publications and source records attributed to Xiong, W.-C..

3 recordsLinked to original sources

bioRxiv2025

Endoplasmic reticulum stress protein GRP78 for ketamine's antidepressant effects

Ketamine is a fast-acting, long-lasting novel antidepressant. However, underpinning intracellular mechanisms remain unclear. We conducted an unbiased screening for genes that were less expressed in the prefrontal cortex (PFC) of mice that did not display antidepression-like effects to ketamine. GO analysis implicated endoplasmic reticulum and protein folding; in particular, GRP78, a stress-induced chaperone protein critical for protein folding, was reduced. We showed that GRP78 deficiency in PFC neurons induced depressive-like behaviors, whereas its overexpression produced anti-depression-like effects, revealing a novel function of GRP78. Prefrontal GRP78 was necessary for ketamines antidepressant-like effects. GRP78 was also required for ketamine to increase calcium activity and glutamatergic transmission. Enhancing GRP78 by viral infection and azoramide enabled non-responsive mice to respond to ketamine. Together, our results demonstrate that GRP78 is critical for ketamine to execute antidepressant effects by potentiating glutamatergic transmission in the PFC. HighlightsO_LIGRP78 was identified in non-biased screens for proteins that were lower in the PFC of mice that failed to exhibit antidepression-like effects after ketamine. C_LIO_LIReducing GRP78 in the PFC induced depressive-like behaviors while increasing GRP78 had opposite effects in wildtype mice. C_LIO_LIGRP78 is required for ketamine to increase calcium activity in excitatory neurons and glutamatergic transmission. C_LIO_LIEnhancing GRP78 by viral infection and by azoramide enabled non-responsive mice to respond to ketamine. C_LI

neuroscience↗

bioRxiv2022

ATP6AP2-to-MMP14, a key pathway for osteoblast to osteocyte transition

Osteocytes, derived from osteoblast (OB)-lineage, occupy lacunae within bone matrix and exhibit unique morphology with dendrite-like projections to form an inter-connected network. Such a network is essential for osteocytes to monitor and orchestrate bone homeostasis. Thus, it is of considerable interest to investigate how osteocytes are formed and how they built the network. Here we provide evidence for ATP6AP2, an accessory subunit of V-ATPase, in OB-lineage cells to be critical for OB-to-osteocyte transition, and osteocyte distribution, maturation, and morphogenesis. Mice (ATP6AP2Ocn-Cre) that selectively deplete ATP6AP2 in OB-lineage cells results in altered osteocyte distribution and morphology, impaired osteocyte maturation and dendrite-like processes, increased osteocyte cell death and cortical woven bone formation. Further mechanistic studies identify MMP14 (matrix metalloproteinase-14) as a critical downstream of ATP6AP2 for osteocyte differentiation. ATP6AP2 interacts with MMP14 and promotes MMP14 surface distribution largely in immature- or osteoid-osteocytes, where this pathway regulates bone matrix remodeling and osteocyte differentiation. Expression of MMP14 into ATP6AP2 knock out OB-lineage cells in the mouse cortical bone could diminish the deficits in osteocyte maturation, dendrite-like process formation, and survival. These results thus demonstrate an un-recognized function of ATP6AP2 in promoting OB-to-osteocyte transition and uncover a pathway from ATP6AP2-to-MMP14 in osteocyte differentiation.

developmental biology↗

bioRxiv2020

Myosin X interaction with KIF13B, a crucial pathway for Netrin-1-induced axonal development

Myosin X (Myo X) transports cargos to the tip of filopodia for cell adhesion, migration, and neuronal axon guidance. Deleted in Colorectal Cancer (DCC) is one of Myo X cargos essential for Netrin-1-regulated axon pathfinding. Myo Xs function in axon development in vivo and the underlying mechanisms remain poorly understood. Here, we provide evidence for Myo Xs function in Netrin-1-DCC regulated axon development in mouse neocortex. Knocking-out (KO) or knocking-down (KD) Myo X in embryonic cortical neurons impairs axon initiation and contralateral branching/targeting. Similar axon deficits are detected in Netrin-1-KO or DCC-KD cortical neurons. Myo X interacts with KIF13B (a kinesin family motor protein), which is induced by Netrin-1. Netrin-1 promotes anterograde transportation of Myo X into axons in KIF13B dependent manner. KIF13B-KD cortical neurons exhibit similar axon deficits. These results suggest Myo X-KIF13B as a critical pathway for Netrin-1 promoted axon initiation and branching/targeting.

developmental biology↗