Sequence and structural insights of monoleucine-based sorting motifs contained within the cytoplasmic domains of basolateral proteins

Sarah J Harmych; Claiborne W Tydings; Jens Meiler; Bhuminder Singh

doi:10.3389/fcell.2024.1379224

Sequence and structural insights of monoleucine-based sorting motifs contained within the cytoplasmic domains of basolateral proteins

Front Cell Dev Biol. 2024 Mar 1:12:1379224. doi: 10.3389/fcell.2024.1379224. eCollection 2024.

Authors

Sarah J Harmych^{1

2}, Claiborne W Tydings³, Jens Meiler^{3

4}, Bhuminder Singh^{1

5}

Affiliations

¹ Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States.
² Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN, United States.
³ Department of Chemistry and Center for Structural Biology, Vanderbilt University, Nashville, TN, United States.
⁴ Institute for Drug Discovery, Leipzig University Medical School, Leipzig, Germany.
⁵ Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, TN, United States.

Abstract

Delivery to the correct membrane domain in polarized epithelial cells is a critical regulatory mechanism for transmembrane proteins. The trafficking of these proteins is directed by short amino acid sequences known as sorting motifs. In six basolaterally-localized proteins lacking the canonical tyrosine- and dileucine-based basolateral sorting motifs, a monoleucine-based sorting motif has been identified. This review will discuss these proteins with an identified monoleucine-based sorting motif, their conserved structural features, as well as the future directions of study for this non-canonical basolateral sorting motif.

Keywords: basolateral sorting motif; clathrin adaptor proteins; epithelial polarity; monoleucine-based motif; polarized protein trafficking.

Publication types

Review

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. We acknowledge funding support to the Singh laboratory by NCI R01CA248505, American Cancer Society—Research Scholar Grant RSG-20-130-01-DDC, and CDMRP W81XWH-21-1-0694. CT is supported by the training grant T32 DK101003. JM is supported by a Humboldt Professorship of the Alexander von Humboldt Foundation. Work in the Meiler laboratory is further supported through the NIH (R01 CA227833, R01 LM013434, S10 OD016216, S10 OD020154, and S10 OD032234).