The range of action of calcium is a major determinant of neuronal excitability and plasticity. A presumed function of dendritic spines, which convey most excitatory input in the brain, is that they compartmentalize calcium, thereby, constituting separated signaling domains for this potent second messenger. We challenge this notion of isolated spine calcium-signaling by showing that mobile endogenous calcium-binding proteins (CaBPs), such as calbindin-D28k (CB) and parvalbumin (PV), which are abundantly expressed in the CNS, can break the spine limit for calcium. In the case of neighboring co-active spines that process slow synaptic calcium signals, substantial amounts of calcium are shuttled into the dendritic shaft where calcium sums up and activates dendritic downstream signaling. Yet, the size of spines is dynamically adjusted in an activity-dependent manner and functional consequences of these morphological changes are largely unclear. We hypothesized that adjusting the spine morphology provides a powerful tool to regulate spatial calcium integration in dendrites. We tested this hypothesis, using an experimentally constrained, kinetic computer model in which spines of cerebellar Purkinje neurons (PNs) were coupled to their parent dendrite by a neck of variable length and diameter. Our results show that, in the presence of CB and PV, the spine neck exerts a substantial influence on spino-dendritc coupling and is a major determinant of biochemical dendritic signal integration and concomitant calmodulin activation. Finally, spines were recently shown to slow down longitudinal dendritic diffusion, leading to a phenomenon known as 'anomalous subdiffusion'. We find, that subdiffusion also occurs in non-spiny dendrites of cortical neurons and, thus, may be a more common phenomenon than hitherto assumed. Functional consequences for dendritic calcium signals, such as those underlying the induction of LTD in PNs, are currently under investigation.