Axon-dendrite and apical-basolateral sorting in a single neuron

Abstract Cells are highly organized machines with functionally specialized compartments. For example, membrane proteins are localized to axons or dendrites in neurons and to apical or basolateral surfaces in epithelial cells. Interestingly, many sensory cells—including vertebrate photoreceptors and...

Full description

Saved in:

Bibliographic Details
Published in:	Genetics (Austin) Vol. 221; no. 1
Main Authors:	Lillis, Monique, Zaccardi, Nathan J, Heiman, Maxwell G
Format:	Journal Article
Language:	English
Published:	United States Oxford University Press 05-05-2022 Genetics Society of America
Subjects:	Animals Axons Axons - metabolism Caenorhabditis elegans - genetics Caenorhabditis elegans - metabolism Compartments Dendrites Dendrites - metabolism Epithelial cells Epithelium Genetics Humans Investigation Localization Mammals Membrane proteins Neural Cell Adhesion Molecule L1 - genetics Neural Cell Adhesion Molecule L1 - metabolism Neurons Neurons - metabolism Olfactory neurons Photoreceptors Proteins Residues Vertebrates apical-basolateral trafficking sensory cells axon-dendrite polarity Caenorhabditis elegans
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Abstract Cells are highly organized machines with functionally specialized compartments. For example, membrane proteins are localized to axons or dendrites in neurons and to apical or basolateral surfaces in epithelial cells. Interestingly, many sensory cells—including vertebrate photoreceptors and olfactory neurons—exhibit both neuronal and epithelial features. Here, we show that Caenorhabditis elegans amphid neurons simultaneously exhibit axon-dendrite sorting like a neuron and apical-basolateral sorting like an epithelial cell. The distal ∼5–10 µm of the dendrite is apical, while the remainder of the dendrite, soma, and axon are basolateral. To determine how proteins are sorted among these compartments, we studied the localization of the conserved adhesion molecule SAX-7/L1CAM. Using minimal synthetic transmembrane proteins, we found that the 91-aa cytoplasmic tail of SAX-7 is necessary and sufficient to direct basolateral localization. Basolateral localization can be fully recapitulated using either of 2 short (10-aa or 19-aa) tail sequences that, respectively, resemble dileucine and Tyr-based motifs known to mediate sorting in mammalian epithelia. The Tyr-based motif is conserved in human L1CAM but had not previously been assigned a function. Disrupting key residues in either sequence leads to apical localization, while “improving” them to match epithelial sorting motifs leads to axon-only localization. Indeed, changing only 2 residues in a short motif is sufficient to redirect the protein between apical, basolateral, and axonal localization. Our results demonstrate that axon-dendrite and apical-basolateral sorting pathways can coexist in a single cell, and suggest that subtle changes to short sequence motifs are sufficient to redirect proteins between these pathways.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1943-2631 0016-6731 1943-2631
DOI:	10.1093/genetics/iyac036