Overview

The Grant lab has long focused on uncovering the fundamental players and mechanisms that produce directed transport between membrane systems in vivo. Our work has focused most intensely on endocytic trafficking, and the intricate functions that allow endosomes to sort and transport cargo to specific destinations within the cell. Endocytic trafficking, the transport of membrane-associated proteins and lipids back and forth between the plasma membrane and endosomes, is a vital mechanism by which cells sense and interact with their environment and is essential to all eukaryotic life. Endocytic transport controls the composition of the plasma membrane, mediates nutrient uptake, and regulates key processes such as cell division, cell migration, cell polarity, antigen processing by the immune system, nervous system activity, and growth factor receptor signaling during development and disease (Grant and Donaldson, 2009).

Our work is unique in that we pioneered the microscopic nematode C. elegans for the analysis of the fundamental biology of endocytic transport, allowing our research group to make repeated discoveries that would prove generalizable to other systems, including human cells. By combining the great technical advantages of advanced C. elegans molecular genetics with cell biological and biochemical methods, our research has provided many new insights into the basic trafficking processes shared by all multicellular animals. Our high throughput genetic screens identified hundreds of genes required for endocytic traffic and the secretory pathway (Balklava et al., 2007). Many of the endocytic regulators that we discovered first are named RME proteins, including RME-1 and RME-8, the analysis of which proved particularly influential. Our most recent work has delved into multiple facets of under-explored biology, with our studies contributing understanding of the formation and maintenance of endosomal microdomains (Norris et al, 2017; Norris and Grant 2020; Norris et al., 2022), endosomal tubule formation and fission (Rodriguez-Polanco et al., 2023), autophagic lysosome reformation (Swords et al., 2024), giant vesicle ejection by stressed neurons (Wang et al., 2023; Cooper et al., 2021; Arnold et al., 2023), and the phagocytic interactions of neighboring cells with emerging neuronal vesicles (Wang et al., 2023), all analyses within the physiological context of the living animal.

Related Publications

A conserved requirement for RME-8/DNAJC13 in neuronal autophagic lysosome reformation Swords SB, Jia N, Norris A, Modi J, Cai Q, Grant BD. A conserved requirement for RME-8/DNAJC13 in neuronal autophagic lysosome reformation. Autophagy. 2024;20(4):792-808. Epub 20231109. doi: 10.1080/15548627.2023.2269028. PubMed PMID: 37942902; PMCID: PMC11062384. [PubMed]

Syndapin and GTPase RAP-1 control endocytic recycling via RHO-1 and non-muscle myosin II Rodriguez-Polanco WR, Norris A, Velasco AB, Gleason AM, Grant BD. Syndapin and GTPase RAP-1 control endocytic recycling via RHO-1 and non-muscle myosin II. Curr Biol. 2023. Epub 20231005. doi: 10.1016/j.cub.2023.09.051. PubMed PMID: 37832552. [PubMed]

Intermediate filaments associate with aggresome-like structures in proteostressed C. elegans neurons and influence large vesicle extrusions as exophers Arnold ML, Cooper J, Androwski R, Ardeshna S, Melentijevic I, Smart J, Guasp RJ, Nguyen KCQ, Bai G, Hall DH, Grant BD, Driscoll M. Intermediate filaments associate with aggresome-like structures in proteostressed C. elegans neurons and influence large vesicle extrusions as exophers. Nat Commun. 2023;14(1):4450. Epub 20230724. doi: 10.1038/s41467-023-39700-1. PubMed PMID: 37488107; PMCID: PMC10366101. [PubMed]

Large vesicle extrusions from C. elegans neurons are consumed and stimulated by glial-like phagocytosis activity of the neighboring cell Wang Y, Arnold ML, Smart AJ, Wang G, Androwski RJ, Morera A, Nguyen KCQ, Schweinsberg PJ, Bai G, Cooper J, Hall DH, Driscoll M, Grant BD. Large vesicle extrusions from C. elegans neurons are consumed and stimulated by glial-like phagocytosis activity of the neighboring cell. Elife. 2023;12. Epub 20230302. doi: 10.7554/eLife.82227. PubMed PMID: 36861960; PMCID: PMC10023159. [PubMed]

Mutagenesis and structural modeling implicate RME-8 IWN domains as conformational control points Norris A, McManus CT, Wang S, Ying R, Grant BD. Mutagenesis and structural modeling implicate RME-8 IWN domains as conformational control points. PLoS Genet. 2022;18(10):e1010296. Epub 20221024. doi: 10.1371/journal.pgen.1010296. PubMed PMID: 36279308; PMCID: PMC9642905. [PubMed]

Stress increases in exopher-mediated neuronal extrusion require lipid biosynthesis, FGF, and EGF RAS/MAPK signaling Cooper JF, Guasp RJ, Arnold ML, Grant BD, Driscoll M. Stress increases in exopher-mediated neuronal extrusion require lipid biosynthesis, FGF, and EGF RAS/MAPK signaling. Proc Natl Acad Sci U S A. 2021;118(36). doi: 10.1073/pnas.2101410118. PubMed PMID: 34475208; PMCID: PMC8433523. [PubMed]

Endosomal microdomains: Formation and function Norris A, Grant BD. Endosomal microdomains: Formation and function. Curr Opin Cell Biol. 2020;65:86-95. Epub 20200401. doi: 10.1016/j.ceb.2020.02.018. PubMed PMID: 32247230; PMCID: PMC7529669. [PubMed]

SNX-1 and RME-8 oppose the assembly of HGRS-1/ESCRT-0 degradative microdomains on endosomes Norris A, Tammineni P, Wang S, Gerdes J, Murr A, Kwan KY, Cai Q, Grant BD. SNX-1 and RME-8 oppose the assembly of HGRS-1/ESCRT-0 degradative microdomains on endosomes. Proc Natl Acad Sci U S A. 2017;114(3):E307-E16. Epub 20170104. doi: 10.1073/pnas.1612730114. PubMed PMID: 28053230; PMCID: PMC5255583. [PubMed]

Pathways and mechanisms of endocytic recycling Grant BD, Donaldson JG. Pathways and mechanisms of endocytic recycling. Nat Rev Mol Cell Biol. 2009;10(9):597-608. doi: 10.1038/nrm2755. PubMed PMID: 19696797; PMCID: PMC3038567. [PubMed]

Genome-wide analysis identifies a general requirement for polarity proteins in endocytic traffic Balklava Z, Pant S, Fares H, Grant BD. Genome-wide analysis identifies a general requirement for polarity proteins in endocytic traffic. Nat Cell Biol. 2007;9(9):1066-73. Epub 20070819. doi: 10.1038/ncb1627. PubMed PMID: 17704769. [PubMed]