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| Neuroscience
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Lorene
M. Lanier, Ph.D.
Assistant Professor, Department of Neuroscience
lanie002@umn.edu
Office: 4-140 MCB
Phone:(612) 626-2399 |
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Axon Guidance & Growth Cone Motility.
We are interested in understanding the fundamental process that determine when, where and how neurons make connections. Forming connections depends on the ability of axons and dendrites to extend into the surrounding tissue. This navigation is accomplished by the growth cone, a highly dynamic structure at the end of developing axons and dendrites. Interestingly, formation of a growth cone is also a key step in neuronal regeneration after injury, suggesting that regeneration may involve recapitulation of some aspects of neuronal development. In the Lanier lab, we are using primary neuronal cultures and a combination of molecular biology, biochemistry, live cell imaging and fluorescent and electron microscopy to identify key components of the growth cone machinery. This information can then be used to develop transgenic mouse models to study growth cone motility and guidance in vivo.
All of the signaling pathways that guide growth cone motility and determine when and how neurons form synapses ultimately depend on dynamic regulation of the cytoskeleton. In other words, cytoskeletal binding/regulatory proteins may be the ultimate convergence points downstream of myriad signaling pathways. Current projects in the Lanier lab focus on two different actin-binding proteins, Arp2/3 and AFAP110/120. We have shown that Arp2/3 is a negative regulator of growth cone translocation (i.e. forward movement) and that inhibiting Arp2/3 significantly enhances axon elongation and decreases axon branching (see Strasser et al. (2004)). Recently, we have developed an acute preparation of neuronal stem cells and are using this preparation to analyze the role of Arp2/3 in neurite initiation. We are also in the process of developing a mouse model to determine the in vivo function of Arp2/3. One tantalizing suggestion is that inhibition of Arp2/3 might facilitate axon outgrowth and regeneration in vivo. A second series of projects focuses on understanding the function of AFAP110/120 in growth cone dynamics and synapse formation. We have shown that AFAP110/120 is highly enriched in the growth cone and in developing dendritic spines. We are currently investigating the role of AFAP in axon branching and dendritic spine formation and are trying to determine if AFAP function is involved in the morphological changes associated with synaptic plasticity.
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Selected Publications
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Strasser, G.A., Abdul Rahim, N., VanderWall, K.A., Gertler, F.B., and Lanier, L. M. (2004).
Arp2/3 is a Negative Regulator of Growth Cone Translocation.
Neuron 43 (1) 89-94. |
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Lebrand, C., Dent, E. W., Strasser, G. A., Lanier, L. M., Krause, M., Svitkina, T. M., Borisy, G. G., and Gertler, F. B. (2004).
Critical role of Ena/VASP proteins for filopodia formation in neurons and in function downstream of netrin-1.
Neuron 42 (1)37-49. |
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Zukerberg, L. R., Patrick, G. N., Nikolic, M., Humbert, S., Wu, C. L., Lanier, L. M., Gertler, F. B., Vidal, M., Van Etten, R. A., and Tsai, L. H. (2000).
Cables links Cdk5 and c-Abl and facilitates Cdk5 tyrosine phosphorylation, kinase upregulation, and neurite outgrowth.
Neuron 26, 633-646. |
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Lanier, L. M., and Gertler, F. B. (2000a). From Abl to actin: Abl tyrosine kinase and associated proteins in growth cone motility.
Curr Opin Neurobiol 10, 80-87. |
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Lanier, L. M. and F. B. Gertler (2000b).
Actin cytoskeleton: thinking globally, actin' locally.
Curr
Biol 10(18):
R655-7 |
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Humbert, S., Lanier, L. M., and Tsai, L. H. (2000). Synaptic localization of p39, a neuronal activator of cdk5.
Neuroreport 11, 2213-2216. |
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Sabo, S. L., L. M. Lanier, A. F. Ikin, O. Khorkova,
S. Sahasrabudhe, P. Greengard and J. D. Buxbaum (1999).
Regulation of beta-Amyloid Secretion by FE65, an Amyloid Protein Precursor-binding
Protein.
J Biol
Chem
274(12): 7952-7957 |
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Howell, B. W., L. M. Lanier, R. Frank, F. B. Gertler
and J. A. Cooper (1999).
The disabled 1 phosphotyrosine-binding domain binds to the internalization
signals of transmembrane glycoproteins and to phospholipids.
Mol
Cell Biol
19(7): 5179-88 |
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Ferreira, A., Chin, L. S., Li, L., Lanier, L. M., Kosik, K. S., and Greengard, P. (1998). Distinct roles of synapsin I and synapsin II during neuronal development.
Mol Med 4, 22-28. |
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