Abstract
Dendritic arbors are crucial for nervous system assembly, but the intracellular mechanisms that govern their assembly remain incompletely understood. Here, we show that the dendrites of PVD neurons in Caenorhabditis elegans are patterned by distinct pathways downstream of the DMA-1 leucine-rich transmembrane (LRR-TM) receptor. DMA-1/LRR-TM interacts through a PDZ ligand motif with the guanine nucleotide exchange factor TIAM-1/GEF in a complex with act-4/Actin to pattern higher order 4° dendrite branches by localizing F-actin to the distal ends of developing dendrites. Surprisingly, TIAM-1/GEF appears to function independently of Rac1 guanine nucleotide exchange factor activity. A partially redundant pathway, dependent on HPO-30/Claudin, regulates formation of 2° and 3° branches, possibly by regulating membrane localization and trafficking of DMA-1/LRR-TM. Collectively, our experiments suggest that HPO-30/Claudin localizes the DMA-1/LRR-TM receptor on PVD dendrites, which in turn can control dendrite patterning by directly modulating F-actin dynamics through TIAM-1/GEF.
Highlights
Neurons are highly polarized cells, which comprise a single axon and often elaborately sculpted dendritic arbors
We found that loss of hpo-30/Claudin, tiam-1/guanine nucleotide exchange factors (GEFs) or act-4/Actin suppressed the formation of baobablike dendritic arbors (Figure 3A–E) to the same extent as removal of other genes in the Menorin pathway such as dma-1/leucine-rich repeat (LRR)-TM, sax-7/L1CAM, or lect-2/Chondromodulin II (Salzberg et al, 2013; Dıaz-Balzac et al, 2016)
Protein localization of a LECT-2/Chondromodulin II or SAX-7/ L1CAM reporter is not visibly affected in hpo-30/Claudin, tiam-1/GEF or act-4/Actin mutants (Figure 2—figure supplement 1B,C). These findings suggest that hpo-30/Claudin, tiam-1/GEF and act4/Actin, just like dma-1/LRR-TM, sax-7/L1CAM, or lect-2/Chondromodulin II function genetically downstream of or in parallel to mnr-1/Menorin
Summary
Neurons are highly polarized cells, which comprise a single axon and often elaborately sculpted dendritic arbors. The nervous system is formed by a myriad of specific synaptic connections between neurons and the formation of these connections is influenced by the shape and complexity of dendritic arbors Both genes that act within the developing neurons and in surrounding tissues are crucial to establish distinct dendritic structures during development (Jan and Jan, 2010; Dong et al, 2015; Lefebvre et al, 2015). Defects in dendrite morphology have been found in various neurological disorders (Kaufmann and Moser, 2000; Kulkarni and Firestein, 2012) Both dendritic and axonal morphology is driven by the cytoskeleton and regulators of the cytoskeleton have important functions in neuronal development. F-actin exists in unbranched and branched forms, whereas microtubules are generally unbranched These filament-like polymers are not static, but highly dynamic structures due to the constant association and dissociation of monomers at either end. F-actin and microtubules are important for countless aspects of
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