@article {70139,
	title = {In-situ glial cell-surface proteomics identifies pro-longevity factors in Drosophila},
	journal = {bioRxiv},
	year = {2025},
	month = {2025 Sep 28},
	abstract = {<p>Much focus has shifted towards understanding how glial dysfunction contributes to age-related neurodegeneration due to the critical roles glial cells play in maintaining healthy brain function. Cell-cell interactions, which are largely mediated by cell-surface proteins, control many critical aspects of development and physiology; as such, dysregulation of glial cell-surface proteins in particular is hypothesized to play an important role in age-related neurodegeneration. However, it remains technically difficult to profile glial cell-surface proteins in intact brains. Here, we applied a cell-surface proteomic profiling method to glial cells from intact brains in Drosophila, which enabled us to fully profile cell-surface proteomes in-situ, preserving native cell-cell interactions that would otherwise be omitted using traditional proteomics methods. Applying this platform to young and old flies, we investigated how glial cell-surface proteomes change during aging. We identified candidate genes predicted to be involved in brain aging, including several associated with neural development and synapse wiring molecules not previously thought to be particularly active in glia. Through a functional genetic screen, we identified one surface protein, DIP-β, which is down-regulated in old flies and can increase fly lifespan when overexpressed in adult glial cells. We further performed whole-head single-nucleus RNA-seq, and revealed that DIP-β overexpression mainly impacts glial and fat cells. We also found that glial DIP-β overexpression was associated with improved cell-cell communication, which may contribute to the observed lifespan extension. Our study is the first to apply in-situ cell-surface proteomics to glial cells in Drosophila, and to identify DIP-β as a potential glial regulator of brain aging.Competing Interest StatementThe authors have declared no competing interest.The original mass spectra and the protein sequence databases used for searches have been deposited in the public proteomics repository MassIVE (http://massive.ucsd.edu) (username: MSV000099083; password: glial). These datasets will be made public upon acceptance of the manuscript. Original proteomic data prior to analyses is provided in the Supplementary Table 1. snRNA-seq data has been deposited to NCBI Gene Expression Omnibus (GSE308135).</p>
},
	doi = {10.1101/2025.09.26.678810},
	url = {https://www.biorxiv.org/content/early/2025/09/28/2025.09.26.678810},
	author = {Marques, Madeline P. and Sun, Bo and Park, Ye-Jin and Jackson, Tyler and Lu, Tzu-Chiao and Qi, Yanyan and Harrison, Erin and Wang, Miranda C. and Venkatachalam, Kartik and Pasha, Omar Moussa and Varanasi, Amogh and Carey, Dominique Kiki and Mani, D.R. and Zirin, Jonathan and Qadiri, Mujeeb and Hu, Yanhui and Perrimon, Norbert and Carr, Steven A. and Udeshi, Namrata D. and Luo, Liqun and Li, Jiefu and Li, Hongjie}
}
@article {68418,
	title = {In situ cell-type-specific cell-surface proteomic profiling in mice.},
	journal = {Neuron},
	year = {2022},
	month = {10/2022},
	abstract = {<p>Cell-surface proteins (CSPs) mediate intercellular communication throughout the lives of multicellular organisms. However, there are no generalizable methods for quantitative CSP profiling in specific cell types in vertebrate tissues. Here, we present in situ cell-surface proteome extraction by extracellular labeling (iPEEL), a proximity labeling method in mice that enables spatiotemporally precise labeling of cell-surface proteomes in a cell-type-specific environment in native tissues for discovery proteomics. Applying iPEEL to developing and mature cerebellar Purkinje cells revealed differential enrichment in CSPs with post-translational protein processing and synaptic functions in the developing and mature cell-surface proteomes, respectively. A proteome-instructed in\&nbsp;vivo loss-of-function screen identified a critical, multifaceted role for Armh4 in Purkinje cell dendrite morphogenesis. Armh4 overexpression also disrupts dendrite morphogenesis; this effect requires its conserved cytoplasmic domain and is augmented by disrupting its endocytosis. Our results highlight the utility of CSP profiling in native mammalian tissues for identifying regulators of cell-surface signaling.</p>
},
	issn = {1097-4199},
	doi = {10.1016/j.neuron.2022.09.025},
	author = {Shuster, S Andrew and Li, Jiefu and Chon, URee and Sinantha-Hu, Miley C and Luginbuhl, David J and Udeshi, Namrata D and Carey, Dominique Kiki and Takeo, Yukari H and Xie, Qijing and Xu, Chuanyun and Mani, D R and Han, Shuo and Ting, Alice Y and Carr, Steven A and Luo, Liqun}
}
