Negative regulators of Neuronal polarity

Negative regulators of neuronal polarity means the molecules will inhibit other downstream or upstream molecules which are involved in controlling the Cytoskeleton formation, stability, endocytosis etc. PTEN (Phosphatase and tensin homolog) It is a lipid phosphatase protein which counteracts the enzyme PI3 K (PI3 kinase) by converting PIP3 formed by PI3K into PIP2. Overexpression of this molecule will lead to prevention of PAR 3 localization to neurites and inhibits axon formation. If the PTEN expression is downregulated using SiRNA, then all the neurites becomes axons and there will reduction in dendrite formation. From...

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Neuronal Polarity Introduction

The formation of single axon and multiple dendrites in a neural cell through distribution of specific functions to discrete cellular domains. The neurons undergo complex morphological rearrangements to assemble into neuronal circuits and propagate signals. Hence they start as a round neuronal spheres and gradually adopting a complex morphology by forming one long axon and several shorted dendrites to eventually connect to target cell or other neurons via synapses.  The central importance for the axon formation and the neuronal polarity is the specialized, highly motile cellular compartment at the tips of the growing axons called growth...

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Cytoskeleton Role in Neuronal polarity

Cytoskeleton plays a vital role in both establishing as well as maintaining polarity in neurons. Basically actin filaments and microtubules have the functional properties which make them uniquely suited to determine and regulate polarity in neurons as well as in other polarizing cells. Two basic characteristic features of Actin filament and microtubules in polarity:        The Microtubules rapidly convert the molecular signals into structural changes modulating cell shape.           They possess an intrinsic polarity. Growth cones support the growth by sensing environmental...

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Actin and Microtubules regulators

Actin regulating proteins Basically the actin dynamics are regulated by actin nucleating, severing, branching and bundling proteins. Actin nucleating proteins are Arp 2/3 complex (Lamellipodia) and formins (Filopodia). The Arp 2/3 complex is also very important in the formation of Filopodia as well as dispensable for actin organization in neuronal growth cones.  Growth cone dynamics regulators (directly modulate actin dynamics): WAVE (wiskott Aldrich syndrome protein [WASP] family verprolin homologous protein) Ena/VASP (Vasodilator stimulated phosphoprotein) Profilin ADF (actin depolymerization factor)/ cofilin WAVE protein...

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Neuronal polarity regulation

The hippocampal neurons form a spikes and small proturusion veils at stage 1. This is stage where the neuron stem cell breaks out from the cell cycle. Then the truncated protrusions develop into a several neurites at stage 2.   At stage 3, All the neurites are roughly equal in length, in which only one neurite will start to break the initial morphology symmetry and grows at rapid rate and thus they eshtablish polarity. The extracellular cues can guide which neurite to grow as axon. The extracellular cues are highly concentrated over the stage 2 immature neurites. Well the guidance happens through the help of downstream...

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PAR protein in axon specification and neuronal polarity

Par (for partition defective) proteins are evolutionary conserved proteins, which are involved in regulating axon specification and establishment of neuronal polarity.  These proteins are first discovered in the C.elegans, which has 6 par genes named as par1-6. s. no Par proteins In C.elegans Drosophila homolog Mammalian homolog Involvement in neuronal polarity? 1 Par1 Serine/Threonine kinase Par 1 MARK kinase SAD kinase Yes 2 Par2 Zinc finger and ATP binding motif (ubiquitination pathway) Not conserved Not conserved unknown 3 Par3 ...

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