Proximity proteomics of synaptopodin provides insight into the molecular composition of the spine apparatus of dendritic spines

被引:15
作者
Falahati, Hanieh [1 ,2 ,3 ,4 ]
Wu, Yumei [1 ,2 ,3 ,4 ]
Feuerer, Vanessa [1 ,2 ,3 ,4 ]
Simon, Hans-Georg [5 ,6 ]
De Camilli, Pietro [1 ,2 ,3 ,4 ]
机构
[1] Yale Univ, Dept Neurosci, Sch Med, New Haven, CT 06510 USA
[2] Yale Univ, Dept Cell Biol, Sch Med, New Haven, CT 06510 USA
[3] Yale Univ, HHMI, Sch Med, New Haven, CT 06510 USA
[4] Yale Univ, Program Cellular Neurosci Neurodegenerat & Repair, Sch Med, New Haven, CT 06510 USA
[5] Northwestern Univ, Feinberg Sch Med, Dept Pediat, Chicago, IL 60611 USA
[6] Stanley Manne Childrens Res Inst, Chicago, IL 60611 USA
关键词
spine apparatus; dendritic spine; iBioID; in vivo proximity proteomics; Pdlim7; ACTIN-ASSOCIATED PROTEIN; ALPHA-ACTININ; ENDOPLASMIC-RETICULUM; CEREBRAL-CORTEX; ORGANIZATION; PLASTICITY; PATHOLOGY; LOCALIZATION; ORGANELLE; TARGET;
D O I
10.1073/pnas.2203750119
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The spine apparatus is a specialized compartment of the neuronal smooth endoplasmic reticulum (ER) located in a subset of dendritic spines. It consists of stacks of ER cisterns that are interconnected by an unknown dense matrix and are continuous with each other and with the ER of the dendritic shaft. While this organelle was first observed over 60 y ago, its molecular organization remains a mystery. Here, we performed in vivo proximity proteomics to gain some insight into its molecular components. To do so, we used the only known spine apparatus-specific protein, synaptopodin, to target a biotinylating enzyme to this organelle. We validated the specific localization in dendritic spines of a small subset of proteins identified by this approach, and we further showed their colocalization with synaptopodin when expressed in nonneuronal cells. One such protein is Pdlim7, an actin binding protein not previously identified in spines. Pdlim7, which we found to interact with synaptopodin through multiple domains, also colocalizes with synaptopodin on the cisternal organelle, a peculiar stack of ER cisterns resembling the spine apparatus and found at axon initial segments of a subset of neurons. Moreover, Pdlim7 has an expression pattern similar to that of synaptopodin in the brain, highlighting a functional partnership between the two proteins. The components of the spine apparatus identified in this work will help elucidate mechanisms in the biogenesis and maintenance of this enigmatic structure with implications for the function of dendritic spines in physiology and disease.
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页数:10
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