Higher Spins from Tensorial Charges and OSp(N|2n) Symmetry

It is shown that the quantization of a superparticle propagating in an N=1, D=4 superspace extended with tensorial coordinates results in an infinite tower of massless spin states satisfying the Vasiliev unfolded equations for free higher spin fields in flat and AdS_4 N=1 superspace. The tensorial extension of the AdS_4 superspace is proved to be a supergroup manifold OSp(1|4). The model is manifestly invariant under an OSp(N|8) (N=1,2) superconformal symmetry. As a byproduct, we find that the Cartan forms of arbitrary Sp(2n) and OSp(1|2n) groups are GL(2n) flat, i.e. they are equivalent to flat Cartan forms up to a GL(2n) rotation. This property is crucial for carrying out the quantization of the particle model on OSp(1|4) and getting the higher spin field dynamics in super AdS_4, which can be performed in a way analogous to the flat case.Comment: LaTeX, 21 page (JHEP style), misprints corrected, added comments on the relation of results of hep-th/0106149 with hep-th/9904109 and hep-th/9907113, references adde

Identification of a Novel Synaptic Protein, TMTC3, Involved in Periventricular Nodular Heterotopia with Intellectual Disability and Epilepsy

Defects in neuronal migration cause brain malformations, which are associated with intellectual disability (ID) and epilepsy. Using exome sequencing, we identified compound heterozygous variants (p.Arg71His and p. Leu729ThrfsTer6) in TMTC3, encoding transmembrane and tetratricopeptide repeat containing 3, in four siblings with nocturnal seizures and ID. Three of the four siblings have periventricular nodular heterotopia (PVNH), a common brain malformation caused by failure of neurons to migrate from the ventricular zone to the cortex. Expression analysis using patient-derived cells confirmed reduced TMTC3 transcript levels and loss of the TMTC3 protein compared to parental and control cells. As TMTC3 function is currently unexplored in the brain, we gathered support for a neurobiological role for TMTC3 by generating flies with post-mitotic neuron-specific knockdown of the highly conserved Drosophila melanogaster TMTC3 ortholog, CG4050/tmtc3. Neuron-specific knockdown of tmtc3 in flies resulted in increased susceptibility to induced seizures. Importantly, this phenotype was rescued by neuron-specific expression of human TMTC3, suggesting a role for TMTC3 in seizure biology. In addition, we observed co-localization of TMTC3 in the rat brain with vesicular GABA transporter (VGAT), a presynaptic marker for inhibitory synapses. TMTC3 is localized at VGAT positive pre-synaptic terminals and boutons in the rat hypothalamus and piriform cortex, suggesting a role for TMTC3 in the regulation of GABAergic inhibitory synapses. TMTC3 did not co-localize with Vglut2, a presynaptic marker for excitatory neurons. Our data identified TMTC3 as a synaptic protein that is involved in PVNH with ID and epilepsy, in addition to its previously described association with cobblestone lissencephaly