scholarly journals Gq-mediated calcium dynamics and membrane tension modulate neurite plasticity

2019 ◽  
Author(s):  
Katherine M. Pearce ◽  
Miriam Bell ◽  
Will H. Linthicum ◽  
Qi Wen ◽  
Jagan Srinivasan ◽  
...  

AbstractThe formation and disruption of synaptic connections during development is a fundamental step in neural circuit formation. Subneuronal structures such as neurites are known to be sensitive to the level of spontaneous neuronal activity but the specifics of how neurotransmitter-induced calcium activity regulates neurite homeostasis are not yet fully understood. In response to stimulation by neurotransmitters such as acetylcholine, calcium responses in cells are mediated the Gαq/phospholipase Cβ (PLCβ)/ phosphatidylinositol 4,5 bisphosphate (PI(4, 5)P2) signaling pathway. Here, we show that prolonged Gαq stimulation results in the retraction of neurites in PC12 cells and rupture of neuronal synapses by modulating membrane tension. To understand the underlying cause, we dissected the behavior of individual components of the Gαq/PLCβ/PI(4, 5)P2 pathway during retraction, and correlated these to the retraction of the membrane and cytoskeletal elements impacted by calcium signaling. We developed a mathematical model that combines biochemical signaling with membrane tension and cytoskeletal mechanics, to show how signaling events are coupled to retraction velocity, membrane tension and actin dynamics. The coupling between calcium and neurite retraction is shown to be operative in the C. elegans nervous system. This study uncovers a novel mechanochemical connection between the Gαq/PLCβ/(PI(4, 5)P2 pathway that couples calcium responses with neural plasticity.

2021 ◽  
Vol 22 (10) ◽  
pp. 5113
Author(s):  
Jae-Yeon Kim ◽  
Mercedes F. Paredes

A prolonged developmental timeline for GABA (γ-aminobutyric acid)-expressing inhibitory neurons (GABAergic interneurons) is an amplified trait in larger, gyrencephalic animals. In several species, the generation, migration, and maturation of interneurons take place over several months, in some cases persisting after birth. The late integration of GABAergic interneurons occurs in a region-specific pattern, especially during the early postnatal period. These changes can contribute to the formation of functional connectivity and plasticity, especially in the cortical regions responsible for higher cognitive tasks. In this review, we discuss GABAergic interneuron development in the late gestational and postnatal forebrain. We propose the protracted development of interneurons at each stage (neurogenesis, neuronal migration, and network integration), as a mechanism for increased complexity and cognitive flexibility in larger, gyrencephalic brains. This developmental feature of interneurons also provides an avenue for environmental influences to shape neural circuit formation.


2004 ◽  
Vol 19 (5) ◽  
pp. 1217-1225 ◽  
Author(s):  
Katsushige Sato ◽  
Naohisa Miyakawa ◽  
Yoko Momose-Sato

2012 ◽  
Vol 15 (12) ◽  
pp. 1675-1682 ◽  
Author(s):  
Arantza Barrios ◽  
Rajarshi Ghosh ◽  
Chunhui Fang ◽  
Scott W Emmons ◽  
Maureen M Barr

2013 ◽  
Vol 24 (3) ◽  
pp. 146-155 ◽  
Author(s):  
Marie-Laure Baudet ◽  
Anaïs Bellon ◽  
Christine E. Holt

2002 ◽  
Vol 156 (6) ◽  
pp. 1065-1076 ◽  
Author(s):  
Shoichiro Ono ◽  
Kanako Ono

Tropomyosin binds to actin filaments and is implicated in stabilization of actin cytoskeleton. We examined biochemical and cell biological properties of Caenorhabditis elegans tropomyosin (CeTM) and obtained evidence that CeTM is antagonistic to ADF/cofilin-dependent actin filament dynamics. We purified CeTM, actin, and UNC-60B (a muscle-specific ADF/cofilin isoform), all of which are derived from C. elegans, and showed that CeTM and UNC-60B bound to F-actin in a mutually exclusive manner. CeTM inhibited UNC-60B–induced actin depolymerization and enhancement of actin polymerization. Within isolated native thin filaments, actin and CeTM were detected as major components, whereas UNC-60B was present at a trace amount. Purified UNC-60B was unable to interact with the native thin filaments unless CeTM and other associated proteins were removed by high-salt extraction. Purified CeTM was sufficient to restore the resistance of the salt-extracted filaments from UNC-60B. In muscle cells, CeTM and UNC-60B were localized in different patterns. Suppression of CeTM by RNA interference resulted in disorganized actin filaments and paralyzed worms in wild-type background. However, in an ADF/cofilin mutant background, suppression of CeTM did not worsen actin organization and worm motility. These results suggest that tropomyosin is a physiological inhibitor of ADF/cofilin-dependent actin dynamics.


Author(s):  
Shobhana Sivaramakrishnan ◽  
Ashley Brandebura ◽  
Paul Holcomb ◽  
Daniel Heller ◽  
Douglas Kolson ◽  
...  

Bushy cells (BC) of the cochlear nucleus mono-innervate their target neuron, the principal cell of the medial nucleus of the trapezoid body (MNTB), via the calyx of Held (CH) terminal, which is a typically mammalian structure and perhaps the largest nerve terminal in the brain. CH:MNTB innervation has become an attractive model to study neural circuit formation because it forms quickly, passing through stages of competition in mice within 2–4 days. BCs innervate MNTB neurons by E17, but CHs do not begin to grow for another five days (P3). Progress has been made to identify molecular factors for axon guidance, CH growth, and physiological maturation of synaptic partners, but important details remain to be discovered. We summarize key events in CH formation and highlight unresolved issues in molecular and physiological signaling, roles for non-neural cells, and the nature of competition during the first postnatal week.


2009 ◽  
Vol 05 (01) ◽  
pp. 115-121
Author(s):  
ANDREW R. PARKER ◽  
H. JOHN CAULFIELD

"What comes first: the chicken or the egg?" Eyes and vision were a great concern for Darwin. Recently, religious fundamentalists have started to attack evolution on the grounds that this is a chicken and egg problem. How could eyes improve without the brain module to use the new information that eye provides? But how could the brain evolve a neural circuit to process data not available to it until a new eye capability emerges? We argue that neural plasticity in the brain allows it to make use of essentially any useful information the eye can produce. And it does so easily within the animal's lifetime. Richard Gregory suggested something like this 40 years ago. Our work resolves a problem with his otherwise-insightful work.


2012 ◽  
Vol 23 (10) ◽  
pp. 1917-1927 ◽  
Author(s):  
Jessica M. Shivas ◽  
Ahna R. Skop

The widely conserved Arp2/3 complex regulates branched actin dynamics that are necessary for a variety of cellular processes. In Caenorhabditis elegans, the actin cytoskeleton has been extensively characterized in its role in establishing PAR asymmetry; however, the contributions of actin to the maintenance of polarity before the onset of mitosis are less clear. Endocytic recycling has emerged as a key mechanism in the dynamic stabilization of cellular polarity, and the large GTPase dynamin participates in the stabilization of cortical polarity during maintenance phase via endocytosis in C. elegans. Here we show that disruption of Arp2/3 function affects the formation and localization of short cortical actin filaments and foci, endocytic regulators, and polarity proteins during maintenance phase. We detect actin associated with events similar to early endosomal fission, movement of endosomes into the cytoplasm, and endosomal movement from the cytoplasm to the plasma membrane, suggesting the involvement of actin in regulating processes at the early endosome. We also observe aberrant accumulations of PAR-6 cytoplasmic puncta near the centrosome along with early endosomes. We propose a model in which Arp2/3 affects the efficiency of rapid endocytic recycling of polarity cues that ultimately contributes to their stable maintenance.


2019 ◽  
Vol 7 (1) ◽  
pp. 6 ◽  
Author(s):  
Charlotte Kelley ◽  
Erin Cram

The reproductive system of the hermaphroditic nematode C. elegans consists of a series of contractile cell types—including the gonadal sheath cells, the spermathecal cells and the spermatheca–uterine valve—that contract in a coordinated manner to regulate oocyte entry and exit of the fertilized embryo into the uterus. Contraction is driven by acto-myosin contraction and relies on the development and maintenance of specialized acto-myosin networks in each cell type. Study of this system has revealed insights into the regulation of acto-myosin network assembly and contractility in vivo.


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