spines are known to change shape, to the extend of appearing and
disappearing entirely. It has long been hypothesised that such
changes may be the basis of memory itself (Bailay
& Kandel, 1993;
& Bonhoeffer, 1999;
The elucidation of how these elements of memory are brought about remain
one of the most exciting and important in the whole of biology!
These changes in dendritic spine shape are thought to be mediated by the
actin cytoskeleton (Fifova
& Morales, 1992)
although these details too are far from clear (see below).
modest size, some dendritic spines contain a specialized type of smooth
endoplasmic reticulum organised as stack and referred to my some as
"spine apparatus" (Gray,
1982). Ribosomes too are found in the
spines, and it is considered that this constitutes a mechanism for
getting newly synthesized gene products to the PSD within dendritic
& Worley, 2001).
Specifically a mRNA encoding Arc (activity-regulated
cytoskeleton-associated protein) is localised to synapses that have been
activated. However, mRNA encoding actin is not localised at
dendritic spines with the concentrated protein but it is localised in
the neuronal cell body (Kaech
et al, 1997).
In other cell types actin mRNA is localised at for example the leading
edge at the site of polymerisation (Hoock
et al, 1991).
The localization of actin in dendritic spines is iso-form specific,
forced expression of cardiac a-actin
in hippocampal neurons concentrates in bundles in the dendritic shafts (Kaech
et al, 1997).
actin cytoskeleton of Dendritic Spines
Many actin-binding proteins are known to be concentrated in spines
(table 1). Photobleach recovery data of EGFP-actin in dendtritic
spines indicate that 85% of the actin in dendritic spines is dynamic,
with an average cycle time of 44 seconds (Star
et al, 2002).
Surprisingly, the cycle time of actin was found to be independent of the
size of the spines. If this is correct then the finding suggests that
the architecture of actin in the spines is atypical. Normally,
F-actin filled projections from cells (e.g. microvilli) have
uniform polarity barbed ends abutting the membrane with a bundling
protein gathering the filaments together. The actin cycling time
in these cells is expected to be a function of the bundle length which
would normally in turn be a function of the length of the
projection. Perhaps dendritic spines contain Arp2/3
complexes forming branching networks whose regulation may not be
dependent on the process length. As spines are stimulated with for
example NMDA, calcium flows into the spine (through the NMDA receptor)
and this leads to the slowing of actin cycling. This inhibition is
thought to involve gelsolin as the dendritic spines of gelsolin-null
mice actin cycling in stimulated spine is not slowed to the same extent
How calcium signalling leads to inhibition of actin cycling is not
immediately obvious. However, the actin-filament severing capping
activity of gelsolin (and relatives) is regulated by calcium, pH, other
actin-binding proteins and phosphoinositides (see gelsolin).
The fact that gelsolin regulates the NMDA receptor calcium channel is
also likely to be part of the story (Fukukawa
et al, 1997).
binds cell adhesion proteins and through a-catenin
to the actin cytoskeleton. It has been shown (Murase
et al, 2002),
that depolarization of neurons leads to a change in localization of b-catenin
from the dendritic shaft to the spines where it binds cadherins. These
effects were also found in neurons treated with tyrosine kinase
inhibitors such as genistein but inhibited by inhibitors of tyrosine
phosphatases (orthovanadate), indicating that the b-catenin
redistribution is under the control of a tyrosine kinase pathway. The
net result of this is that synaptic activity increases the strength of
the synapse by increasing the homotypic cadherin dependent adhesion
between the presynaptic terminal and the synapse.
cytoskeletal component of most cells (but not neurons, where
& Morales, 1992
kelch containing actin-binding protein.
et al, 2002
spectrin-actin interactions and bundles F-actin.
et al, 2001
actin filament bundling protein
actin filaments to cell adhesion proteins through a-catenin
et al, 2002
myosin II and calmodulin binding protein
et al, 2000
binding and myosin modulating protein
et al, 2000
dependent protein kinase IIb
& bundling proteins
& Lubec, 2002
& Morales, 1992
& Morales, 1992
1. Proteins enriched in
Agassandian, C., Plantier, M., Fattoum,
A., A, R. & Der Terrosian, E. (2000) Subcellular distribution of
calponin and caldesmon in rat hippocampus. Brain Res. 887,
& Kandel, E.R. (1993) Structural changes accompanying memory
storage. Annu.Rev.Physiol. 55, 397-426.
Bartsch, D., & Kandel, E.R. (1996) Towards a molecular definition of
long-term memory storage. PNAS 93, 13445-13452.
Blanpied, T. A., Scott, D. B. &
Ehlers, M. D. (2002) Dynamics and regulation of clathrin coats at
specialized endocytic zones of dendrites and spines. Neuron. 36,
Dekker-Ohno, K. (1996) Endoplasmic
reticulum is missing in dendritic spines of Purkinje cells of the ataxic
mutant rat., Brain Res. 714, 226-230.
Egert, F. &
Bonhoeffer, T (1999) Dendritic spine changes associated with hippocampal
long-term storage. Nature 399, 66-70.
E. & Morales, M. (1992) Actin matrix of dendritic spines, synaptic
plasticity, and long-term potentiation, Int.Rev.Cytol. 139,
Furukawa, K. & al, e. (1997) The
actin-severing protein gelsolin modulates calcium channel and NMDA
receptor activities and vulnerability to excitotoxicity in hippocampal
neurons. J.Neuroscience. 17, 8178-8186.
(1982). Trends Neuroscience 5, 5-6.
Hoock, T. C., Newcomb, P. M.
& Herman, I. M. (1991) b-actin
and its mRNA are localized at the plasma membrane and the regions of
moving cytoplasm during the cellular response to injury, J.Cell Biol.
Hurvitz, H., Gillis, R., Klaus, S.,
Klar, A., Gross-Kieselstein, F. & Okon, E. (1993) A kindred with
Griscelli disease: spectrum of neurological involvement., Eur. J.
Pediatr. 152, 402-405.
Kaech, S., Fischer, M., Doll, T. &
Matus, A. (1997) Isoform specificity in the relatinship of actin to
dendritic spines. J.Neuroscience. 17, 9565-9572.
Brinkhaus, H. & Matus, A. (1999) Volatile anesthetics block
actin-based motility in dendritic spines. PNAS. 96, 10433-10437.
Kaech, S., Parmar, H., Roelandse, M.,
Bornmann, C. & Matus, A. (2001) Cytoskeletal microdifferentiation: A
mechanism for organizing morphological plasticity in dendrites. PNAS.
Li, X. & Bennett, V. (2001) Adducin is an in vivo substrate
for protein kinase C: Phosphorylation in the MARKS-related domain
inhibits activity in promoting spectrin-actin complexes and occurs in
many cells, including dendritic spines of neurons. J.Cell Biol. 142,
Bernhardt, R. & Hugh-Jones, T. (1981) PNAS, 78, 3010-3014.
Marase, S., Mosser, E. &
Schuman, E. M. (2002) Depolarization drives b-catenin
into neuronal spines promoting changes in synaptic structure and
function. Neuron. 35, 91-105.
Maravall, M.M. & Svoboda, K. (2001) Ca2+ signalling in
dendritic spines. Curr.Op.Neurobiol. 11, 349-356.
Sanchez, C., Ulloa, L., Montoro, R.
J., Lopez-Barneo, J. & Avila, J. (1997) NMDA-glutamate receptors
regulate phosphorylation of dendritic cytoskeletal proteins in the
hippocampus. Brain Res. 765, 141-148.
Teruel, M. N., Subramanian, K. & Meyer, T. (1998) CaMKIIb fundtions
as an F-actin targeting module that localizes CaMKIIa/b heterooligomers
to dendritic spines., Neuron. 21, 593-606.
Shim, K. S.
& Lubec, G. (2002) Drebrin, a dendritic spine protein, is manifold
decreased in brains of patients with Alzheimer's disease and Down
syndrome. Neuroscience Lett. 324, 209-212.
Star, E. N., Kwiatkowski, D. J. &
Murthy, V. N. (2002) Rapid turnover of actin in dendritic spines and its
regulation by activity. Nature Neuroscience. 5, 239-246.
Stewart, O. & Worley, P. F. (2001)
A cellular mechanism for targeting newly synthesized mRNAs to synaptic
site on dendrites., PNAS. 98, 7062-7068.
Takagishi, Y., Oda, S., Hayasaka, S.,
Dekker Ohno, K., Shikata, T. & Inouye, M. (1996) The dilute-lethal (d(I))
gene attacks a Ca2+ store in the dendritic spine of Purkinje
cells in mice., Neuroscience Lett. 215, 169-172.
Wyszynski, M., Lin, J., Rao, A.,
Nigh, E., Beggs, A. H., Craig, A. M. & Sheng, M. (1997) Competitive
binding of a-actinin
and calmodulin to the NMDA receptor., Nature. 385, 439-442.
Yuste, R. & Bonhoeffer, T. (2001)
Morphological changes in dendritic spines associated with long-term
synaptic plasticity., Annu.Rev.Neurosci. 24, 1071-1089.
Zito, K. & Murthy, V.N. (2002)
Dendritic spines. Curr.Biol. 12, R5.