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However, a physiological role for Shrm4 daating the brain is yet to be established. Here, we report that Shrm4 is localized to synapses where it regulates dendritic spine morphology and interacts with the C terminus of GABAB receptors GABABRs to control their cell surface expression and intracellular trafficking via a dynein-dependent mechanism.

Our data highlights a role for Shrm4 in synaptogenesis and in maintaining GABABR-mediated inhibition, perturbation of which may be responsible for the involvement of Shrm4 in cognitive disorders and epilepsy. There are four evolutionarily conserved Shrm proteins Shrm 2 that are localized to polarized tissues, including neurons 13. Shrm4 is buiriied expressed throughout embryonic and adult murine brains 2 and also binds to F-actin in non-neuronal cells 4. In addition, a pathogenic missense mutation was identified in an unrelated large family, with carriers exhibiting mild-to-severe intellectual disability ID and increased susceptibility to seizures 25.

Recent studies reinforce the role of Shrm4 in ID 678however, how disruption of KIAA causes these neuropathological conditions is unknown. Indeed, the role of Shrm4 in the brain is also unknown, but given the pathological profile, it may regulate GABA-mediated inhibition 9 The Tye of these receptors is emphasized pa, dysfunction, which occurs in different neurological disease dahing However, the motor-protein-dependent trafficking of these receptors is not fully understood. Our study suggests a possible underlying mechanism by pzm Shrm4 may be involved in epilepsy and ID. Whithey using electron microscopy and post-embedding whltney methods with an anti-Shrm4 antibody 2gold nanoparticles were identified in pre- and post-synaptic areas and along dendrites Supplementary Raacine.

Biochemical fractionation of adult rat brain hippocampi and cortices revealed enrichment of Shrm4 in the postsynaptic density PSD fraction further confirming its presence at synapses Supplementary Fig. To explore the role s of Shrm4 in neurons, we searched for binding partners using yeast two-hybrid Y2H screening. Figure 1: Twenty positive clones were isolated; buirid encoded for a aa stretch of the GABABR subunit 1 C-terminal tail both isoforms 1a and 1b. Transmembrane domains. Error-bars are s.

Scale bar, 0. Hodgson did standup in the s and was apparently considered for the role of Woody in Cheers. After MST3K was cancelled, Hodgson and other collaborators on the show launched a similar venture called Cinematic Titanic, which went on indefinite hiatus as of February His first feature film was the remake of Dawn of the Dead. Man of Steel hits theaters in June. Zack Snyder was born in Green Bay. He grew up in Connecticut where his mom was a painter and photography teacher who encouraged him to study nude paintings as a boy. But it certainly seems comic books and graphic novels had a bigger influence on Snyder. Tom Welling is best known for playing young Clark Kent on the television show Smallville, which is a Superman origin story.

His most recent role is in the film Parkland, in which he plays a real-life secret service agent, Roy Kellerman, who was protecting JFK the day of his assassination. Welling has also worked on the other side of the camera, directing episodes of Smallville and producing the show Hellcats. Les Paul — Waukesha The world owes a debt of gratitude to Wisconsin — because without Les Paul — music as we know it would not be the same. Les Paul is the man credited with inventing the solid-body electric guitar. As a kid, Less Paul would perform at area drive-ins. Steve Miller also happens to be a protege of Les Paul.

Steve Miller says both his parents were musically inclined and loved jazz. Paul encourage young Steve to keep at it and mentored him over the years. He left college before graduating and got an education from the Chicago blues scene instead. Before becoming a TV analyst, she practiced law in Wisconsin as well. Despite her success, she still makes time for friends from Wisconsin. Greta recently posted on her blog, GretaWire about teasing a junior high girlfriend, and in an interview with ClassicWisconsin. Snyder, who passed away inis one of the unsung heroes of late night television. He grew up in Milwaukee and went to Marquette University where he first planned to study medicine, but switched to journalism because of his love of radio and broadcasting.

Tomorrow was cancelled to make way for a young man named David Letterman. But there were no hard feelings between the two hosts. Snyder was known for his in-depth and personal interviews. Watch a grumpy Gene Simmons and a hilariously inebriated Ace Frehly in the clip below. However, she was also involved in theater and while at UW she met Tony Shalhoub. As the story goes, he encouraged her to pursue acting, and Jane followed Tony to the Yale School of Drama. Kate set Jane up on a date with Bradley Whitford, a fellow Wisconsinite and actor. The two were married for 17 years, but filed for divorce in Although she never won, Kaczmarek was nominated for seven Emmy awards and three Golden Globes for her work on Malcolm in the Middle.

The Josh Lyman character may have been a perfect fit for Whitford. Whitford has also had his share of film roles, including big movies like Philadelphia, Scent of a Woman and Awakenings. As you can see in the clip below — he did get to put his classical training from Julliard to good use. Fiedler was born in Platteville, and moved to Shorewood at the age of five. His dad happened to be a beer salesman.

Fiedler died of cancer in just one day after good friend and fellow Winnie the Pooh star Racune Winchell passed away. Winchell provided the voice of Teh. But if you grew up in the s, you might be more interested to know that the voice of Hwitney the Duck came from Wisconsin. The movie was nominated for seven Golden Raspberry awards and won Worst Picture bulried On the brighter side, Chip Zien more recently played heroic airplane passenger Mark Rothenberg in the film United Of course, the character of Sloth was loveable while also deformed.

Okay maybe you can Coincidentally, the idea for man-hands not the entire script was sold to the show by an elementary school teacher in Green Bay. And I mean very short lived. The sitcom was canceled after one episode. Kristin Bauer van Straten was born in Racine, and has a lot of good things to say about her home-state on her website. The movie was screened at the Green Bay Film Festival. During college he performed with a local group called The Indigos. His professional musical career started out in northern California nightclubs, eventually he moved to L.

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Among his many hits is the theme song to the show Moonlighting. That led to one of his Grammy awards. Besides his Grammy awards, the renowned jazz singer is also known for his scatting abilities. Allen Ludden — Mineral Point Allen Ludden made a name for himself hosting various game shows — most notably, Password, from to He lived in a few different Wisconsin cities before his mother and adoptive stepfather moved the family to Texas. But he never forgot his connection to the state. Ludden was buried next to his biological father who died of influenza at the age of At one point the two hosted a talk show together. It was shot shortly after Ludden and White got married.

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