The spine apparatus (SA) is an essential component of mature dendritic spines of cortical and hippocampal neurons, yet its functions are still enigmatic. Synaptopodin (SP), an actin-binding protein, colocalizes with the SA. Hippocampal neurons in SP-knockout mice lack SA, and they express lower LTP. SP probably plays a role in synaptic plasticity, but only recently it is being linked mechanistically to synaptic functions. These authors and others have studied endogenous and transfected SP in dendritic spines of cultured hippocampal neurons. They found that spines containing SP generate twice as large responses to flash photolysis of caged glutamate than SP-negative ones. An N-methyl-d-aspartate receptor—mediated chemical LTP caused accumulation of GFP-GluR1 in spine heads of control but not of shRNA transfected, SP-deficient neurons. SP is linked to calcium stores, because their pharmacological blockade eliminated SP-related enhancement of glutamate responses. Furthermore, release of calcium from stores produces an SP-dependent delivery of GluR1 into spines. Thus, SP plays a crucial role in the calcium store-associated ability of neurons to undergo long-term plasticity.
Asanuma K., Yanagida-Asanuma E., Faul C., Tomino Y., Kim K., Mundel P.2006. Synaptopodin orchestrates actin organization and cell motility via regulation of RhoA signaling. Nat Cell Biol8:485-91.
2.
Asanuma K., Kim K., Oh J., Giardino L., Chabanis S., Faul C., and others. 2005. Synaptopodin regulates the actin-bundling activity of alpha-actinin in an isoform-specific manner. J Clin Invest115:1188-98.
3.
Auerbach JM, Segal M.1994. A novel cholinergic induction of long-term potentiation in rat hippocampus. J Neurophysiol72:2034-40.
4.
Bas Orth C., Vlachos A., Del Turco D., Burbach GJ, Haas CA, Mundel P., and others. 2005. Lamina-specific distribution of synaptopodin, an actin-associated molecule essential for the spine apparatus, in identified principal cell dendrites of the mouse hippocampus. J Comp Neurol487:227-39.
5.
Bas Orth C., Schultz C., Müller CM, Frotscher M., Deller T.2007. Loss of the cisternal organelle in the axon initial segment of cortical neurons in synaptopodin-deficient mice. J Comp Neurol504:441-9.
6.
Cummings JA, Mulkey RM, Nicoll RA, Malenka RC1996. Ca2+ signaling requirements for long term depression in the hippocampus. Neuron, 16:825-33.
7.
Czarnecki K., Haas CA, Bas Orth C., Deller T., Frotscher M.2005. Postnatal development of synaptopodin expression in the rodent hippocampus. J Comp Neurol490:133-44.
8.
Deller T., Orth CB, Del Turco D., Vlachos A., Burbach GJ, Drakew A., and others. 2007. A role for synaptopodin and the spine apparatus in hippocampal synaptic plasticity. Ann Anat189:5-16.
9.
Deller T., Korte M., Chabanis S., Drakew A., Schwegler H., Stefani GG, and others. 2003. Synaptopodin-deficient mice lack a spine apparatus and show deficits in synaptic plasticity. Proc Natl Acad Sci U S A100:10494-9.
10.
Deller T., Merten T., Roth SU, Mundel P., Frotscher M.2000. Actin-associated protein synaptopodin in the rat hippocampal formation: localization in the spine neck and close association with the spine apparatus of principal neurons. J Comp Neurol418:164-81.
11.
Dudek SM, Bear MF1993. Bidirectional long term modification of synaptic effectiveness in the adult and immature hippocampus. J Neurosci13:2910-18.
12.
Emptage N., Bliss TV, Fine A.1999. Single synaptic events evoke NMDA receptor-mediated release of calcium from internal stores in hippocampal dendritic spines. Neuron22: 115-24.
13.
Fifkova E., Markham JA, Delay RJ1983. Calcium in the spine apparatus of dendritic spines in the dentate molecular layer. Brain Res266:163-8.
14.
Fischer M., Kaech S., Wagner U., Brinkhaus H., Matus A.2000. Glutamate receptors regulate actin-based plasticity in dendritic spines. Nat Neurosci3:887-94.
Fukazawa Y., Saitoh Y., Ozawa F., Ohta Y., Mizuno K., Inokuchi K.2003. Hippocampal LTP is accompanied by enhanced F-actin content within the dendritic spine that is essential for late LTP maintenance in vivo . Neuron38:447-460.
17.
Gray EG1959. Axo-somatic and axo-dendritic synapses of the cerebral cortex: an electron microscope study. J Anat93:420-33.
18.
Harvey J., Collingridge GL1992. Thapsigargin blocks the induction of long-term potentiation in rat hippocampal slices. Neurosci Lett139:197-200.
19.
Ivenshitz M., Segal M.2006. Simultaneous NMDA-dependent long-term potentiation of EPSCs and long-term depression of IPSCs in cultured rat hippocampal neurons . J Neurosci26:1199-210.
20.
Jedlicka P., Schwarzacher SW, Winkels R., Kienzler F., Frotscher M., Bramham CR, and others. 2009. Impairment of in vivo theta-burst long-term potentiation and network excitability in the dentate gyrus of synaptopodin-deficient mice lacking the spine apparatus and the cisternal organelle. Hippocampus19:130-40.
21.
Korkotian E., Segal M.2007. Morphological constraints on calcium dependent glutamate receptor trafficking into individual dendritic spine. Cell Calcium42(1):41-57.
22.
Kovalchuk Y., Eilers J., Lisman J., Konnerth A.2000. NMDA receptor-mediated subthreshold Ca(2+) signals in spines of hippocampal neurons. J Neurosci20:1791-9.
23.
Kremerskothen J., Plaas C., Kindler S., Frotscher M., Barnekow A.2005. Synaptopodin, a molecule involved in the formation of the dendritic spine apparatus, is a dual actin/alpha-actinin binding protein . J Neurochem92:597-606.
24.
Martin ED, Buno W.2003. Caffeine-mediated presynaptic long term potentiation in hippocampal CA1 pyramidal neurons. J Neurophysiol89:3029-3038.
25.
Matsuzaki M., Honkura N., Ellis-Davies GC, Kasai H.2004. Structural basis of long-term potentiation in single dendritic spines. Nature429:761-6.
26.
Meldolesi J.2001. Rapidly exchanging Ca2+ stores in neurons: molecular, structural and functional properties. Prog Neurobiol65:309-38.
27.
Mundel P., Heid HW, Mundel TM, Kruger M., Reiser J., Kriz W.1997. Synaptopodin: an actin-associated protein in telencephalic dendrites and renal podocytes. J Cell Biol139:193-204.
28.
Okubo-Suzuki R., Okada D., Sekiguchi M., Inokuchi K.2008. Synaptopodin maintains the neural activity-dependent enlargement of dendritic spines in hippocampal neurons. Mol Cell Neurosci38:266-76.
29.
Pilpel Y., Segal M.2004. Activation of PKC induces rapid morphological plasticity in dendrites of hippocampal neurons via Rac and Rho-dependent mechanisms. Eur J Neurosci19:3151-64.
30.
Richards DA, de Paola V., Caroni P., Gahwiler BH, McKinney RA2004. AMPA receptor activation regulates the diffusion of a membrane marker in parallel with dendritic spine motility in the mouse hippocampus . J Physiol558(Pt 2):503-12.
31.
Roth SU, Sommer C., Mundel P., Kiessling M.2001. Expression of synaptopodin, an actin-associated protein, in the rat hippocampus after limbic epilepsy. Brain Pathol11: 169-81.
32.
Sajikumar S., Li Q., Abraham WC, Xiao ZC2009. Priming of short term potentiation and synaptic tagging/capture mechanisms by ryanodine receptor activation in rat hippocampal CA1. Learning Memory16:178-186.
33.
Shimuta M., Yoshikawa M., Fukaya M., Watanabe M., Takeshima H., Manabe T.2001. Postsynaptic modulation of AMPA receptor mediated synaptic responses and LTP by the type 3 Ryanodine receptor. Mol Cell Neurosci17:921-30.
34.
Spacek J.1985. Three-dimensional analysis of dendritic spines. II. Spine apparatus and other cytoplasmic components. Anat Embryol ( Berl) 171(2):235-43.
35.
Spacek J., Harris KM1997. Three-dimensional organization of smooth endoplasmic reticulum in hippocampal CA1 dendrites and dendritic spines of the immature and mature rat. J Neurosci17:190-203.
36.
Trommer BL, Kennelly JJ, Colley PA, Overstreet LS, Slater NT, Pasternak JF1995. AP5 blocks LTP in developing rat dentate gyrus and unmasks LTD. Exp Neurol13:83-92.
37.
Vlachos A., Maggio N., Segal M.2008. Lack of correlation between synaptopodin expression and the ability to induce LTP in the rat dorsal and ventral hippocampus. Hippocampus18(1):1-4.
38.
Vlachos A., Korkotian E., Schonfeld E., Copanaki E., Deller T., Segal M.2009. Synaptopodin regulates plasticity of dendritic spines in hippocampal neurons. J Neurosci29: 1017-1033.
39.
Welsby P.Rowan M., Anwyl R.2006. Nicotinic receptor-mediated enhancement of long term potentiation involves activation of metabotropic glutamate receptors and ryanodine-sensitive calcium stores in the dentate gyrus. Eur J Neurosci24:3109-3118.
40.
Wyszynski M., Lin J., Rao A., Nigh E., Beggs AH, Craig AM, and others. 1997. Competitive binding of alpha-actinin and calmodulin to the NMDA receptor. Nature385:439-42
41.
Wynzynski M., Kharazia V., Shanghvi R., Rao A., Beggs AH, Craig AM, and others. 1998. Differential regional expression and ultrasctructural localization of alpha-actinin-2, a putative NMDA receptor-anchoring protein, in rat brain. J Neurosci18:1383-92
42.
Yamazaki M., Matsuo R., Fukazawa Y., Ozawa F., Inokuchi K.2001. Regulated expression of an actin-associated protein, synaptopodin, during long-term potentiation. J Neurochem79:192-9.
