Evidence for a satellite secretory pathway in neuronal dendritic spines

Abstract

Long-term information storage within the brain requires the synthesis of new proteins and their use in synapse-specific modifications [1]. Recently, we demonstrated that translation sites for the local synthesis of integral membrane and secretory proteins occur within distal dendritic spines [2]. It remains unresolved, however, whether a complete secretory pathway, including Golgi and trans Golgi network-like membranes, exists near synapses for the local transport and processing of newly synthesized proteins. Here, we report evidence of a satellite secretory pathway in distal dendritic spines and distal dendrites of the mammalian brain. Membranes analogous to early (RER and ERGIC), middle (Golgi cisternae), and late (TGN) secretory pathway compartments are present within dendritic spines and in distal dendrites. Local synthesis, processing, and transport of newly translated integral membrane and secretory proteins may thus provide the molecular basis for synapse-specific modifications during long-term information storage in the brain.

Paxillin Associates with Poly(A)-binding Protein 1 at the Dense Endoplasmic Reticulum and the Leading Edge of Migrating Cells

“…8A). One of these is in the NH 2 terminus (residues [17][18][19][20][21][22][23][24][25][26][27][28][29][30], and the other is nearer to the COOH-terminal end of the protein (residues 345-358) (Fig. 8, A and B).…”

“…PABP1 binds with high affinity to the dendritic localizer sequence in the 3Ј-UTR of the vasopressin mRNA (21) and may be involved in targeting mRNA to polyribosomes on peripherally located ER elements (20). On iodixanol gradients, paxillin and PABP1 are present in substantial quantities in the dense, polyribosomal ER.…”

“…His-PABP1 was eluted with a buffer containing 100 mM EDTA at 4°C and dialyzed against PBS, pH 7.4. PCR-amplified DNA fragments corresponding to the LD1 (aa [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20], LD2 (aa 141-160), LD3 (aa 212-231), LD4 (aa 263-282), and LD5 (aa 299 -317) motifs of human paxillin-␣ were subcloned into the BamHI-EcoRI site of the pGEX-2TK vector (26), as previously reported (6). The construct encoding chick paxillin residues 54 -313 in the pGEX-2T vector was a generous gift from Dr. Chris Turner (SUNY, Syracuse, NY).…”

“…Recently, it has been shown that a satellite secretory pathway containing elements of the rough endoplasmic reticulum, the endoplasmic reticulum-Golgi interstitial compartment and Golgi that are necessary to locally translate and process these secretory proteins, is present in dendritic spines (20). The 3Ј-UTR of the vasopressin mRNA contains sequences responsible for localizing it to dendrites, termed the "dendritic localizer sequence" (19).…”

Protein Kinase D Controls the Integrity of Golgi Apparatus and the Maintenance of Dendritic Arborization in Hippocampal Neurons

“…A thread-like and reticular structure of the Golgi apparatus has been already described in many neuronal types (Takamine et al, 2000;Fujita and Okamoto, 2005;Horton et al, 2005). Central neuronal Golgi complex is localized in the soma and often extends into the principal dendrites, but Golgi elements were also found as discontinuous structures in the distal dendrites, often near synaptic contacts or in dendritic spines (Gardiol et al, 1999;Pierce et al, 2001;Sytnyk et al, 2002;Horton and Ehlers, 2003). The dispersed localization of the Golgi apparatus indicates unique spatial regulation of the neuronal secretory pathway compared with other mammalian cells.…”