AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |
Back to Blog
Show picture of dendrite and axon2/27/2024 ![]() Surprisingly, changing these sequences to typical dileucine or YxxΦ motifs re-directs their localization from basolateral to axon-only. These basolateral sequences contain Ile-Leu and Tyr residues that are required for their function, but they do not conform to typical dileucine or Tyr-based motifs. Here, by analyzing the localization of a minimal synthetic transmembrane protein in a single sensory neuron in vivo, we identify 2 short cytoplasmic sequences that are sufficient to direct basolateral localization. 2019), providing a unique opportunity to directly compare apical-basolateral and axon-dendrite sorting in a single cell. Recently, we discovered that sensory neurons in Caenorhabditis elegans exhibit epithelial characteristics including apical-basolateral polarity ( Low et al. Defining the relationship between the mechanisms that govern protein sorting in neurons and epithelial cells may reveal how such complicated subcellular organization evolved from simple apical-basolateral polarity. Previous work has identified a wide variety of mechanisms for polarized localization of neuronal proteins, including local translation, transcytosis, selective retention, and many others ( Bentley and Banker 2016). In principle, neuronal proteins are likely to require more complex trafficking mechanisms, as they are often localized to specific subcompartments within axons (the axon initial segment, nodes of Ranvier, or presynaptic sites) or dendrites (proximal or distal branches or specific classes of postsynaptic spines) ( Donato et al. However, further investigation revealed a more complicated relationship, with some basolateral proteins localizing uniformly to axons and dendrites rather than in a polarized manner ( Silverman et al. Initial studies suggested that neurons use the same sorting mechanisms as epithelial cells because epithelial proteins with known basolateral motifs localized to dendrites when mis-expressed in neurons ( Bentley and Banker 2016). Neurons are highly compartmentalized cells whose major surfaces-axons and dendrites-have different protein compositions. However, as these studies were conducted in homogeneous cultured epithelial cells, it remains unclear how proteins are trafficked in vivo in cells with more complex organization. ![]() Classical studies identified short cytoplasmic sequences that are responsible for basolateral sorting, namely dileucine (xxxL) and tyrosine (Tyr)-based motifs (YxxΦ or NPxY) ( Duffield et al. To achieve these cell-surface differences, many transmembrane proteins contain sequences that are recognized by sorting machinery in the secretory pathway in order to direct the proteins to their appropriate destinations. 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.Ī cell presents many faces to the world: for example, the outward-facing (apical) surface of an epithelial cell is decorated with transmembrane proteins that are different from those on its inward-facing (basolateral) surface, reflecting the specialized functions of each compartment. Indeed, changing only 2 residues in a short motif is sufficient to redirect the protein between apical, basolateral, and axonal localization. Disrupting key residues in either sequence leads to apical localization, while “improving” them to match epithelial sorting motifs leads to axon-only localization. The Tyr-based motif is conserved in human L1CAM but had not previously been assigned a function. 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. Using minimal synthetic transmembrane proteins, we found that the 91-aa cytoplasmic tail of SAX-7 is necessary and sufficient to direct basolateral localization. To determine how proteins are sorted among these compartments, we studied the localization of the conserved adhesion molecule SAX-7/L1CAM. The distal ∼5–10 µm of the dendrite is apical, while the remainder of the dendrite, soma, and axon are basolateral. Here, we show that Caenorhabditis elegans amphid neurons simultaneously exhibit axon-dendrite sorting like a neuron and apical-basolateral sorting like an epithelial cell. Interestingly, many sensory cells-including vertebrate photoreceptors and olfactory neurons-exhibit both neuronal and epithelial features. For example, membrane proteins are localized to axons or dendrites in neurons and to apical or basolateral surfaces in epithelial cells. Cells are highly organized machines with functionally specialized compartments.
0 Comments
Read More
Leave a Reply. |