Novel and Conserved Protein Macoilin Is Required for Diverse Neuronal Functions in Caenorhabditis elegans

Abstract

Neural signals are processed in nervous systems of animals responding to variable environmental stimuli. This study shows that a novel and highly conserved protein, macoilin (MACO-1), plays an essential role in diverse neural functions in Caenorhabditis elegans. maco-1 mutants showed abnormal behaviors, including defective locomotion, thermotaxis, and chemotaxis. Expression of human macoilin in the C. elegans nervous system weakly rescued the abnormal thermotactic phenotype of the maco-1 mutants, suggesting that macoilin is functionally conserved across species. Abnormal thermotaxis may have been caused by impaired locomotion of maco-1 mutants. However, calcium imaging of AFD thermosensory neurons and AIY postsynaptic interneurons of maco-1 mutants suggest that macoilin is required for appropriate responses of AFD and AIY neurons to thermal stimuli. Studies on localization of MACO-1 showed that C. elegans and human macoilins are localized mainly to the rough endoplasmic reticulum. Our results suggest that macoilin is required for various neural events, such as the regulation of neuronal activity.

Identification of 526 Conserved Metazoan Genetic Innovations Exposes a New Role for Cofactor E-like in Neuronal Microtubule Homeostasis

“…(B) Pan-neuronal expression of D2092.5 (maco-1) , ortholog of macoilin, a transmembrane and coiled-coil domain-containing protein. Our data are consistent with studies published during the course of our investigation that showed neuronal-specific expression pattern for this protein and an involvement in neuronal functions in C. elegans [42], [43], motoneurons (mns) in the ventral nerve cord are indicated. (C) Neuronal-specific expression of C15C8.4, homolog of LRPAP1 a low-density lipoprotein receptor-related protein tentatively associated with degenerative dementia [77].…”

“…Importantly, a number of core metazoan genes have been recently characterized (Table S3); these genes are associated with the nervous system, developmental function and human disease. For example, consistent with our expression analysis showing pan-neuronal distribution, macoilin/ maco-1 has been shown to be involved in regulating neuronal functions in C. elegans [42], [43]. Another recently characterized metazoan-specific gene is TTC19/ ddl-3 .…”

dnc-1/dynactin 1 Knockdown Disrupts Transport of Autophagosomes and Induces Motor Neuron Degeneration

“…The worms were allowed to settle for 30 s, their movements were captured by video for 30 s, and the number of thrashing movements was counted. We also analyzed the speed of movement using a video capture system as described previously [22]. Briefly, fully matured, adult worms were transferred individually to agar plates with no food.…”

Thermotaxis of C. elegans as a model for temperature perception, neural information processing and neural plasticity

“…These results suggest that MACO-1 is generally required for neuronal excitability and synapse organization 59 , 60 . FLJ10747, a predicted human homolog of MACO-1, rescued the thermotaxis defects of maco-1 mutants, 59 indicating that the function of macoilin is evolutionary conserved between nematodes and humans. Thus, the functional identifications of MACO-1 in C. elegans provided important clues for the analysis of human macoilin.…”

“…The maco-1/ttx-8 gene, encoding a homolog of human macoilin, was originally isolated as thermotaxis defective mutant and independently as suppressor for social behavior defective mutants 59 , 60 . MACO-1 is a highly conserved novel protein with several transmembrane domains in the N-terminus and coiled-coil domains in the C-terminus.…”