© The Rockefeller University Press,
0021-9525/1998//795 $5.00
The Journal of Cell Biology, Volume 143, Number 3,
, 1998 795-813
Paralemmin, a Prenyl-Palmitoyl–anchored Phosphoprotein Abundant in Neurons and Implicated in Plasma Membrane Dynamics and Cell Process Formation
Christian Kutzleb*,
Gabriele Sanders*,
Raina Yamamoto*,
Xiaolu Wang*,
Beate Lichte*,
Elisabeth Petrasch-Parwez
, and
Manfred W. Kilimann*
* Institut für Physiologische Chemie, and Institut für Anatomie, Ruhr-Universität Bochum, D-44780 Bochum, Germany
We report the identification and initial characterization of paralemmin, a putative new morphoregulatory protein associated with the plasma membrane. Paralemmin is highly expressed in the brain but also less abundantly in many other tissues and cell types. cDNAs from chicken, human, and mouse predict acidic proteins of 42 kD that display a pattern of sequence cassettes with high inter-species conservation separated by poorly conserved linker sequences. Prenylation and palmitoylation of a COOH-terminal cluster of three cysteine residues confers hydrophobicity and membrane association to paralemmin. Paralemmin is also phosphorylated, and its mRNA is differentially spliced in a tissue-specific and developmentally regulated manner. Differential splicing, lipidation, and phosphorylation contribute to electrophoretic heterogeneity that results in an array of multiple bands on Western blots, most notably in brain. Paralemmin is associated with the cytoplasmic face of the plasma membranes of postsynaptic specializations, axonal and dendritic processes and perikarya, and also appears to be associated with an intracellular vesicle pool. It does not line the neuronal plasmalemma continuously but in clusters and patches. Its molecular and morphological properties are reminiscent of GAP-43, CAP-23, and MARCKS, proteins implicated in plasma membrane dynamics. Overexpression in several cell lines shows that paralemmin concentrates at sites of plasma membrane activity such as filopodia and microspikes, and induces cell expansion and process formation. The lipidation motif is essential for this morphogenic activity. We propose a function for paralemmin in the control of cell shape, e.g., through an involvement in membrane flow or in membrane–cytoskeleton interaction.
Key Words: farnesylation • lipidation • cortical cytoskeleton • membrane traffic • synapse
Abbreviations used in this paper: GFP, green fluorescent protein; GST, glutathione-S-transferase; nt, nucleotide(s); RT-PCR, reverse-transcribed polymerase chain reaction; SNARE, SNAP receptor.
Address all correspondence to Manfred W. Kilimann, Institut für Physiologische Chemie, Ruhr-Universität Bochum, D-44780 Bochum, Germany. Tel.: 49-234-700-7927. Fax: 49-234-7094-193. E-mail: manfred.kilimann{at}ruhr-uni-bochum.de
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Facebook 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
-
Arstikaitis, P., Gauthier-Campbell, C., Carolina Gutierrez Herrera, R., Huang, K., Levinson, J. N., Murphy, T. H., Kilimann, M. W., Sala, C., Colicos, M. A., El-Husseini, A.
(2008). Paralemmin-1, a Modulator of Filopodia Induction Is Required for Spine Maturation. Mol. Biol. Cell
19: 2026-2038
[Abstract]
[Full Text]
-
Lane, K. T., Beese, L. S.
(2006). Thematic review series: Lipid Posttranslational Modifications. Structural biology of protein farnesyltransferase and geranylgeranyltransferase type I. J. Lipid Res.
47: 681-699
[Abstract]
[Full Text]
-
van Erp, K., Dach, K., Koch, I., Heesemann, J., Hoffmann, R.
(2006). Role of strain differences on host resistance and the transcriptional response of macrophages to infection with Yersinia enterocolitica. Physiol. Genomics
25: 75-84
[Abstract]
[Full Text]
-
Gauthier-Campbell, C., Bredt, D. S., Murphy, T. H., El-Husseini, A. E.-D.
(2004). Regulation of Dendritic Branching and Filopodia Formation in Hippocampal Neurons by Specific Acylated Protein Motifs. Mol. Biol. Cell
15: 2205-2217
[Abstract]
[Full Text]
-
Tyas, D. A., Pearson, H., Rashbass, P., Price, D. J.
(2003). Pax6 Regulates Cell Adhesion during Cortical Development. Cereb Cortex
13: 612-619
[Abstract]
[Full Text]
-
Takemoto-Kimura, S., Terai, H., Takamoto, M., Ohmae, S., Kikumura, S., Segi, E., Arakawa, Y., Furuyashiki, T., Narumiya, S., Bito, H.
(2003). Molecular Cloning and Characterization of CLICK-III/CaMKIgamma , a Novel Membrane-anchored Neuronal Ca2+/Calmodulin-dependent Protein Kinase (CaMK). J. Biol. Chem.
278: 18597-18605
[Abstract]
[Full Text]
-
Chauhan, B. K., Reed, N. A., Zhang, W., Duncan, M. K., Kilimann, M. W., Cvekl, A.
(2002). Identification of Genes Downstream of Pax6 in the Mouse Lens Using cDNA Microarrays. J. Biol. Chem.
277: 11539-11548
[Abstract]
[Full Text]
-
Wang, X., Herberg, F. W., Laue, M. M., Wullner, C., Hu, B., Petrasch-Parwez, E., Kilimann, M. W.
(2000). Neurobeachin: A Protein Kinase A-Anchoring, beige/Chediak-Higashi Protein Homolog Implicated in Neuronal Membrane Traffic. J. Neurosci.
20: 8551-8565
[Abstract]
[Full Text]
-
Frey, D., Laux, T., Xu, L., Schneider, C., Caroni, P.
(2000). Shared and Unique Roles of Cap23 and Gap43 in Actin Regulation, Neurite Outgrowth, and Anatomical Plasticity. JCB
149: 1443-1454
[Abstract]
[Full Text]
-
El-Husseini, A. E., Craven, S. E., Chetkovich, D. M., Firestein, B. L., Schnell, E., Aoki, C., Bredt, D. S.
(2000). Dual Palmitoylation of Psd-95 Mediates Its Vesiculotubular Sorting, Postsynaptic Targeting, and Ion Channel Clustering. JCB
148: 159-172
[Abstract]
[Full Text]
-
Wang, X., Kibschull, M., Laue, M. M., Lichte, B., Petrasch-Parwez, E., Kilimann, M. W.
(1999). Aczonin, a 550-Kd Putative Scaffolding Protein of Presynaptic Active Zones, Shares Homology Regions with Rim and Bassoon and Binds Profilin. JCB
147: 151-162
[Abstract]
[Full Text]
-
El-Husseini, A. E.-D., Craven, S. E., Brock, S. C., Bredt, D. S.
(2001). Polarized Targeting of Peripheral Membrane Proteins in Neurons. J. Biol. Chem.
276: 44984-44992
[Abstract]
[Full Text]
