Molecular and Cellular Neurobiology

The area of molecular and cellular neurobiology is defined more by the methods and approaches used in research than by the specific types of questions being asked, except that the questions address structure, function and mechanisms of neuronal cells. Studies are being performed on cultured rodent neurons, organotypic brain slices and genetic mutant mice (Bamburg, Hentges, Partin, Tamkun, Tobet), on mammalian nervous system tissues (Bamburg, Rash, Tobet), on crustaceans during molting (Mykles) and on different developmental stages of Drosophila (Reist). Studies examine the ultrastructure of synapses, membrane receptors and junctions (Rash, Reist), the distribution and function of various receptors within the CNS (Bamburg, Hentges, Mykles, Partin, Tamkun, Tobet), molecular mechanisms of synaptic function including synaptic plasticity (Bamburg,Hentges, Partin, Rash, Reist, Tamkun), cytoskeletal regulation of membrane receptors, growth cone pathfinding and synaptic function (Bamburg, Reist, Tamkun, Tobet), and transmembrane signaling pathways regulating many different cellular processes in nervous system development and function. Recent articles in the area of cellular and molecular neurobiology from different faculty laboratories and links to the faculty home pages are given below.

 

Bamburg: The role and regulation of the actin cytoskeleton is studied in many aspects of neuronal differentiation, development, function and degeneration using primary neuronal cultures and organotypic hippocampal slice cultures.

Huang TY, Minamide LS, Bamburg JR, Bokoch GM. Chronophin serves as an ATP-sensing mechanism for cofilin dephosphorylation and neuronal cofilin-actin rod formation. Dev Cell 15, 691-703 (2008). PMID:19000834

Lee CW, Han J, Bamburg JR, Han L, Lynn R, Zheng JQ. Regulation of acetylcholine receptor clustering by ADF/cofilin-directed vesicular trafficking. Nat Neurosci 12, 848-856 (2009). PMID: 19483689

 

Hentges: Transgenic and knock-out mice are used to study neurons in the hypothalamus that regulate food intake. At the cellular and molecular level, we examine changes in mRNA, receptor expression and coupling, and plasticity in transmitter phenotype.

Hentges ST, Low MJ, Williams JT. Differential regulation of synaptic inputs by constitutively released endocannabinoids and exogenous cannabinoids. J Neurosci 25, 9746-9751 (2005). PMID: 16237178

Hentges ST, Otero-Corchon V, Pennock RL, King CM, Low MJ. Proopiomelanocortin expression in both GABA and glutamate neurons. J Neurosci 29,13684-13690 (2009). PMID: 19864580

 

Mykles: The effects of molting on the expression of neuropeptides in the central nervous system of crustaceans.

Lee KJ, Kim HW, Gomez AM, Chang ES, Covi JA, Mykles, DL. Molt-inhibiting hormone from the tropical land crab, Gecarcinus lateralis: cloning, tissue expression, and expression of biologically active recombinant peptide in yeast. Gen Comp Endocrinol. 150, 505-513 (2007). PMID: 17094991

Zarubin TP, Chang ES, Mykles DL. Expression of recombinant eyestalk crustacean hyperglycemic hormone from the tropical land crab, Gecarcinus lateralis, that inhibits Y-organ ecdysteroidogenesis in vitro. Mol Biol Rep. 36, 1231–1237 (2009). PMID: 18595002

 

Partin: The structure and function of AMPA receptor gating and its modulation, and the cell trafficking of receptors in neurons, using molecular and structural biology, confocal imaging, and patch clamp electrophysiology.

Bedoukian MA, Whitesell JD, Peterson EJ, Clay CM, Partin, K.M. The stargazin C terminus encodes an intrinsic and transferable membrane sorting signal. J Biol Chem. 283, 1597-1600 (2008). PMID: 17986442

Jin R, Clark S, Weeks AM, Dudman J, Gouaux E, Partin, K.M. Molecular mechanism of positive allosteric modulators acting on AMPA receptor. J Neurosci 25, 9027-9036 (2005). PMID: 16192394

 

Rash: Using confocal immunofluorescence microscopy and freeze-fracture replica immunogold labeling (FRIL) electron microscopy, we are investigating the composition and molecular architecture of neuronal and glial plasma membranes in goldfish, mosquitofish, mouse, rat, and human CNS and PNS.

Meier C, Dermietzel R, Davidson KGV, Yasumura T, Rash JE. Connexin32-containing gap junctions in Schwann cells at the internodal zone of myelin compaction and in Schmidt- Lanterman incisures. J Neurosci 24, 3186-3198 (2004). PMID: 15056698

Rash JE, Davidson KGV, Kamasawa N, Yasumura T, Kamasawa M, Zhang C, Michaels R, Restrepo D, Ottersen OP, Olson C, Nagy JI. Ultrastructural localization of connexins (Cx36, Cx43, Cx45), glutamate receptors and aquaporin-4 in rodent olfactory mucosa, olfactory nerve and olfactory bulb. J Neurocytol 34, 307-341 (2005). PMID: 16841170

 

Reist: The power of Drosophila genetics are applied to examine the molecular mechanisms of synaptic transmission. Molecular biology, electron microscopy, electrophysiology, immunohistochemistry, and protein chemistry are used to analyze the function of individual proteins in regulating synaptic vesicles.

Loewen CA, Lee SM, Shin YK, Reist, N.E. Synaptotagmin's C2B Polylysine Motif Facilitates a Ca2+-Independent Stage of Synaptic Vesicle Priming In vivo. Molec Biol Cell 17, 5211-5226 (2006). PMID: 16987956.

Paddock BE, Striegel A, Hui E, Chapman ER, Reist NE. Ca2+-Dependent, Phospholipid-Binding Residues of Synaptotagmin are Critical for Excitation-Secretion Coupling. J Neurosci. 28, 7458-7466 (2008). PMID: 18650324.

 

Tamkun: Studies on the mechanisms underlying voltage-gated ion channel trafficking, localization and activity on the neuronal cell surface. Combinations of live cell fluorescence microscopy, single molecule tracking, and electrophysiology are used.

Tamkun MM, O'Connell KMS, Rolig AS. A cytoskeletal-based perimeter fence selectively corrals a sub-population of cell surface Kv2.1 channels. J Cell Sci 120, 2413-2423 (2007). PMID: 17606996

Sarmiere PD, Weigle CM, Tamkun MM. The Kv2.1 K+ channel targets to the axon initial segment of hippocampal and cortical neurons in culture and in situ. BMC Neuroscience. 9, 112 (2008). PMID: 19014551

 

Tobet: The role of cell signaling during neuronal migration is studied in mouse brain.

Knoll JG, Wolfe CA, Tobet SA. Estrogen modulates neuronal movements within the developing preoptic area/anterior hypothalamus. Eur J Neurosci. 26,1091-1099 (2007). PMID: 17767488

McClellan KM, Calver AR, Tobet SA. GABAB Receptors role in cell migration and positioning within the ventromedial nucleus of the hypothalamus. Neuroscience 151, 1119-1131 (2008). PMID: 18248902