The Hoogenraad group moved to the University of Utrecht

http://web.science.uu.nl/cellbiology/index.php?option=com_content&view=article&id=8&Itemid=5 

 We focus on the interface of cell biology and neuronal plasticity. Our work is directed at understanding intracellular protein trafficking in neurons and its relationship with synapse formation and function.

The brain is a network of electrically active neurons that communicate with each other via synapses. Chemical synapses are asymmetric contacts formed between axons of the presynaptic neuron and dendritic specializations of the postsynaptic cell. In excitatory synapses, the presynaptic terminal usually releases the neurotransmitter glutamate, which diffuses across the synaptic cleft to bind to, and activate, glutamate receptors in the postsynaptic membrane. Glutamate receptors are concentrated in a specific electron-dense region of the postsynaptic membrane known as the postsynaptic density (PSD).

Throughout development and adult life, the brain responds to experience by modifying the strength of synapses and changing the number of synapses. It is widely believed that learning and memory through out life is mediated by long-lasting modifications in synaptic strength. In recent years it has become evident that an important way to alter the strength of synaptic transmission is to change the structure and chemistry of synapses and by the formation of new synapses. Since synapses have a key role in information processing and storage, it is important to understand the molecular and cellular mechanisms that control synapse formation/elimination and synaptic strength.

Because of the dynamic alterations of synapses, neurons need a substantially regulated mechanism to deliver and remove synaptic proteins to synaptic sites. For example, neurotransmitter vesicles have to be transported al the way through the axon and delivered to the presynaptic terminal. In constrast glutamate receptors move through dendrites and are inserted into the postsynaptic membrane. The movements of synaptic proteins are crucial for neuronal viability and synaptic function, and can cause neurodegeneration and neuronal death when they are disrupted. We are interested to find out which molecular mechanisms are important for the delivery and removal of synaptic proteins. Therefore, studying the cell biology of synaptic protein trafficking is critical to understanding the molecular mechanisms underlying synaptic plasticity and learning and memory. Such knowledge is also relevant for insight into neurological diseases.

To see the specific projects that are being addressed in the lab go to my website http://homepage.neuro.nl/hoogenraad

Selected recent publications (pubmed)

• Hoogenraad CC, Feliu-Mojer MI, Spangler SA, Milstein AD, Dunah AW, Hung AY, Sheng M (2007). Liprina1 degradation by CaMKII regulates LAR receptor tyrosine phosphatase distribution and dendrite development. Dev Cell 12(4):587-602 (pubmed) 
• Sheng M, Hoogenraad CC (2007) The Postsynaptic Architecture of Excitatory Synapses: A More Quantitative View. Annu Rev Biochem 7 (76):823-847 (pubmed)
• Hoogenraad CC, Milstein AD, Ethell IM, Henkemeyer M, Sheng M. (2005) GRIP1 controls dendrite morphogenesis by regulating EphB receptor trafficking. Nat Neurosci. 8(7):906-15 (pubmed)
• Hoogenraad CC, Wulf P, Schiefermeier N, Stepanova T, Galjart N, Small JV, Grosveld F, de Zeeuw CI, Akhmanova A (2003) Bicaudal D induces selective dynein-mediated microtubule minus end-directed transport. EMBO J. 2003 Nov 17;22(22):6004-15 (pubmed)
• Matanis T, Akhmanova A, Wulf P, Del Nery E, Weide T, Stepanova T, Galjart N, Grosveld F, Goud B, De Zeeuw CI, Barnekow A, Hoogenraad CC. (2002) Bicaudal-D regulates COPI-independent Golgi-ER transport by recruiting the dynein-dynactin motor complex. Nature Cell Biology 4:986-92 (pubmed)
• Hoogenraad CC, Akhmanova A, Howell SA, Dortland BR, De Zeeuw CI, Willemsen R, Visser P, Grosveld F, Galjart N. (2001) Mammalian Golgi-associated Bicaudal-D2 functions in the dynein-dynactin pathway by binding to both complexes. EMBO J 20(15):4041-54. (pubmed)